bluuebunny/crossref_metadata_2025_split huggingface dataset:
The sixth international RASopathies symposium: Precision medicine—From promise to practice
Authors: Gripp Karen W. , Schill Lisa , Schoyer Lisa , Stronach Beth , Bennett Anton M. , Blaser Susan , Brown Amanda , Burdine Rebecca , Burkitt‐Wright Emma , Castel Pau , Darilek Sandra , Dias Alwyn , Dyer Tuesdi , Ellis Michelle , Erickson Gregg , Gelb Bruce D. , Green Tamar , Gross Andrea , Ho Alan , Holder James Lloyd , Inoue Shin‐Ichi , Jelin Angie C. , Kennedy Annie , Klein Richard , Kontaridis Maria I. , Magoulas Pilar , McConnell Darryl B. , McCormick Frank , Neel Benjamin G. , Prada Carlos E. , Rauen Katherine A. , Roberts Amy , Rodriguez‐Viciana Pablo , Rosen Neal , Rumbaugh Gavin , Sablina Anna , Solman Maja , Tartaglia Marco , Thomas Angelica , Timmer William C. , Venkatachalam Kartik , Walsh Karin S. , Wolters Pamela L. , Yi Jae‐Sung , Zenker Martin , Ratner Nancy 
Published: December 2019

AbstractThe RASopathies are a group of genetic disorders that result from germline pathogenic variants affecting RAS‐mitogen activated protein kinase (MAPK) pathway genes. RASopathies share RAS/MAPK pathway dysregulation and share phenotypic manifestations affecting numerous organ systems, causing lifelong and at times life‐limiting medical complications. RASopathies may benefit from precision medicine approaches. For this reason, the Sixth International RASopathies Symposium focused on exploring precision medicine. This meeting brought together basic science researchers, clinicians, clinician scientists, patient advocates, and representatives from pharmaceutical companies and the National Institutes of Health. Novel RASopathy genes, variants, and animal models were discussed in the context of medication trials and drug development. Attempts to define and measure meaningful endpoints for treatment trials were discussed, as was drug availability to patients after trial completion.
A novel homozygous nonsense mutation of VPS13B associated with previously unreported features of Cohen syndrome
Authors: Koehler Katrin , Schuelke Markus , Hell Anna K. , Schittkowski Michael , Huebner Angela , Brockmann Knut 
Published: December 2019

AbstractCohen syndrome (CS) is a rare autosomal recessive disorder associated with mutations in the vacuolar protein sorting 13 homolog B (VPS13B; formerly COH1) gene. The core clinical phenotype comprises a characteristic facial gestalt, marked developmental delay, and myopia. Additional, nonobligatory features include obesity, microcephaly, short stature, muscular hypotonia, scoliosis, narrow hands and feet, progressive retinopathy, as well as neutropenia. Here we report a novel homozygous nonsense mutation in the VPS13B gene and previously undescribed clinical features in a 19‐year‐old woman with developmental delay, intellectual disability, and a particular facial appearance. The patient showed several features consistent with CS. In addition, the parents observed congenital alacrima and anhidrosis persisting until onset of puberty. The diagnosis was not established based on the clinical phenotype. We performed whole‐genome sequencing and identified a novel homozygous nonsense mutation c.62T>G (NM_152564.4), p.(Leu21*) in the VPS13B gene. Our findings extended the previously reported phenotype of CS. We conclude that transient, prepubertal alacrima and anhidrosis are part of the phenotypic spectrum of CS associated with a novel homozygous nonsense mutation in the VPS13B gene.
Biosynthesis of the N–N‐Bond‐Containing Compound l‐Alanosine
Authors: Wang Menghua , Niikura Haruka , He Hai‐Yan , Daniel‐Ivad Phillip , Ryan Katherine S. 
Published: December 2019

AbstractThe formation of a N−N bond is a unique biochemical transformation, and nature employs diverse biosynthetic strategies to activate nitrogen for bond formation. Among molecules that contain a N−N bond, biosynthetic routes to diazeniumdiolates remain enigmatic. We here report the biosynthetic pathway for the diazeniumdiolate‐containing amino acid l‐alanosine. Our work reveals that the two nitrogen atoms in the diazeniumdiolate of l‐alanosine arise from glutamic acid and aspartic acid, and we clarify the early steps of the biosynthetic pathway by using both in vitro and in vivo approaches. Our work demonstrates a peptidyl‐carrier‐protein‐based mechanism for activation of the precursor l‐diaminopropionate, and we also show that nitric oxide can participate in non‐enzymatic diazeniumdiolate formation. Furthermore, we demonstrate that the gene alnA, which encodes a fusion protein with an N‐terminal cupin domain and a C‐terminal AraC‐like DNA‐binding domain, is required for alanosine biosynthesis.
Tweaking Nickel with Minimal Silver in a Heterogeneous Alloy of Decahedral Geometry to Deliver Platinum‐like Hydrogen Evolution Activity
Authors: Majee Rahul , Kumar Arun , Das Tisita , Chakraborty Sudip , Bhattacharyya Sayan 
Published: December 2019

AbstractFive‐fold intertwined AgxNi1−x (x=0.01–0.25) heterogeneous alloy nanocrystal (NC) catalysts, prepared through unique reagent combinations, are presented. With only ca. 5 at % Ag (AgNi‐5), Pt‐like activity has been achieved at pH 14. To reach a current density of 10 mA cm−2 the extremely stable AgNi‐5 requires an overpotential of 24.0±1.2 mV as compared to 20.1±0.8 mV for 20 % Pt/C, both with equal catalyst loading of 1.32 mg cm−2. The turnover frequency (TOF) is as high as 2.1 H2 s−1 at 50 mV (vs. RHE). Site‐specific elemental analyses show the Ag:Ni compositional variation, where the apex and edges of the decahedra are Ag‐rich, thereby exposing Ni onto the faces to achieve maximum charge transport for an exceptional pH universal HER activity. DFT calculations elucidate the relative H‐atom adsorption capability of the Ni centers as a function of their proximity to Ag atom.
A Quantitative Model for Alkane Nucleophilicity Based on C−H Bond Structural/Topological Descriptors
Authors: Besora Maria , Olmos Andrea , Gava Riccardo , Noverges Bárbara , Asensio Gregorio , Caballero Ana , Maseras Feliu , Pérez Pedro J. 
Published: December 2019

AbstractA first quantitative model for calculating the nucleophilicity of alkanes is described. A statistical treatment was applied to the analysis of the reactivity of 29 different alkane C−H bonds towards in situ generated metal carbene electrophiles. The correlation of the recently reported experimental reactivity with two different sets of descriptors comprising a total of 86 parameters was studied, resulting in the quantitative descriptor‐based alkane nucleophilicity (QDEAN) model. This model consists of an equation with only six structural/topological descriptors, and reproduces the relative reactivity of the alkane C−H bonds. This reactivity can be calculated from parameters emerging from the schematic drawing of the alkane and a simple set of sums.
Amperometric Measurements and Dynamic Models Reveal a Mechanism for How Zinc Alters Neurotransmitter Release
Authors: Ren Lin , Oleinick Alexander , Svir Irina , Amatore Christian , Ewing Andrew G. 
Published: December 2019

AbstractZinc, a suspected potentiator of learning and memory, is shown to affect exocytotic release and storage in neurotransmitter‐containing vesicles. Structural and size analysis of the vesicular dense core and halo using transmission electron microscopy was combined with single‐cell amperometry to study the vesicle size changes induced after zinc treatment and to compare these changes to theoretical predictions based on the concept of partial release as opposed to full quantal release. This powerful combined analytical approach establishes the existence of an unsuspected strong link between vesicle structure and exocytotic dynamics, which can be used to explain the mechanism of regulation of synaptic plasticity by Zn2+ through modulation of neurotransmitter release.
A Molecular Chameleon for Mapping Subcellular Polarity in an Unfolded Proteome Environment
Authors: Owyong Tze Cin , Subedi Pramod , Deng Jieru , Hinde Elizabeth , Paxman Jason J. , White Jonathan M. , Chen Weisan , Heras Begoña , Wong Wallace W. H. , Hong Yuning 
Published: December 2019

AbstractEnvironmental polarity is an important factor that drives biomolecular interactions to regulate cell function. Herein, a general method of using the fluorogenic probe NTPAN‐MI is reported to quantify the subcellular polarity change in response to protein unfolding. NTPAN‐MI fluorescence is selectively activated upon labeling unfolded proteins with exposed thiols, thereby reporting on the extent of proteostasis. NTPAN‐MI also reveals the collapse of the host proteome caused by influenza A virus infection. The emission profile of NTPAN‐MI contains information of the local polarity of the unfolded proteome, which can be resolved through spectral phasor analysis. Under stress conditions that disrupt different checkpoints of protein quality control, distinct patterns of dielectric constant distribution in the cytoplasm can be observed. However, in the nucleus, the unfolded proteome was found to experience a more hydrophilic environment across all the stress conditions, indicating the central role of nucleus in the stress response process.
Valorization of mixed radish seed oil and Prunus armeniaca L. oil as a promising feedstock for biodiesel production: Evaluation and analysis of biodiesels
Authors: Fadhil Abdelrahman B. , Nayyef Akram W. , Sedeeq Saba H. 
Published: December 2019

AbstractA blend of radish oil (RO) and apricot kernel oil (AKO) was transesterified with methanol, ethanol, and their equivalent mixture, to yield methylic biodiesel (MBD), ethylic biodiesel (EBD), and methylic/ethylic biodiesel (MEBD), respectively with the refining of the so‐developed fuels through adsorption onto the activated carbon prepared by ZnCl2 activation of apricot shells. The best conversion of RO–AKO blend to MBD (96.12 ± 1.25%) and MEBD (94.23 ± 2.22) was attained at KOH concentration, 0.75% w/w of oil, alcohol/oil molar ratio, 6/1, mixing intensity, 600 rpm, reaction temperature, 60°C, and 45‐min reaction period, whereas the best conditions that produced the highest yield of EBD (95.19 ± 2.0 %) were KOH concentration, 1.0 KOH % w/w of oil, ethanol/oil molar ratio, 8/1, mixing intensity, 600 rpm, reaction temperature, 65°C, and 75‐min reaction period. The Fourier‐transform infrared spectroscopy and 1H nuclear magnetic resonance confirmed formation of the alkyl esters from the RO–AKO blend. The quality of MBD, EBD, and MEBD obtained from the RO–AKO blend was evaluated and found comparable with the American Society for Testing and Materials (ASTM) D6751 standards. Additionally, blending of MEBD with petrodiesel was possible, and properties of the blends were in accordance with those established by ASTM D7467‐17. The methanolysis of the RO–AKO mixture followed the pseudo‐first‐order kinetics with activation energy of 27.27 kJ mol−1. In conclusion, the RO–AKO mixture could be low‐cost feedstock for biodiesel production. Moreover, apricot shells could be exploited as a priceless and suitable adsorbent for the adsorption of impurities found in the crude alkyl esters for its high surface area.
Anatomy and Flight Performance of the Early Enantiornithine Bird Protopteryx fengningensis: Information from New Specimens of the Early Cretaceous Huajiying Formation of China
Authors: Chiappe Luis M. , Di Liu , Serrano Francisco J. , Yuguang Zhang , Meng Qingjin 
Published: December 2019

ABSTRACTThe Early Cretaceous (∼131 Million Years Ago) Protopteryx fengningensis is one of the oldest and most primitive enantiornithine birds; however, knowledge of its anatomy has largely been limited to the succinct description of two specimens (holotype and paratype). This study describes two new specimens of P. fengningensis preserving most of the skeleton and plumage, and it therefore adds significantly to understanding the morphology of this important species and the character evolution of enantiornithine birds. The well‐preserved plumage of these specimens also affords a quantitative assessment of the flight performance of P. fengningensis. Our aerodynamic considerations indicate that this early enantiornithine was capable of intermittent flight (bounding or flap‐gliding), thus marking the earliest occurrence of such energy‐saving aerial strategy. Anat Rec, 303:716–731, 2020. © 2019 American Association for Anatomy
Design partnerships for participatory librarianship: A conceptual model for understanding librarians co designing With digital youth
Authors: Yip Jason C. , Lee Kung Jin , Lee Jin Ha 
Published: December 2019

AbstractLibraries play a central role for youth and digital learning. As libraries transition to learning spaces, youth librarians can engage in aspects of democratic design that empowers youth. Participatory design (PD) is a user‐centered design method that can support librarians in the democratic development of digital learning spaces. However, while PD has been used in libraries, we have little knowledge of how youth librarians can act as codesign partners. We need a conceptual model to understand the role of youth librarians in codesign, and how their experiences are integrated into youth design partnerships. To generate this model, we examine a case study of the evolutionary process of a single librarian and the development of a library system's learning activities through PD. Using the idea of equal design partnerships, we analyzed video recordings and stakeholder interviews on how children (ages 7–11) worked together with a librarian to develop new digital learning activities. Our discussion focuses on the development of a participatory librarian design conceptual model that situates librarians as design partners with youth. The article concludes with recommendations for integrating PD methods into libraries to create digital learning spaces and suggestions for moving forward with this design perspective.
Neonatal Thyroid Stimulating Hormone and Subsequent Diagnosis of Autism Spectrum Disorders and Intellectual Disability
Authors: Ames Jennifer L. , Windham Gayle C. , Lyall Kristen , Pearl Michelle , Kharrazi Martin , Yoshida Cathleen K. , Van de Water Judy , Ashwood Paul , Croen Lisa A. 
Published: December 2019

Hypothyroid conditions in early life, if left untreated, are associated with adverse neurodevelopmental outcomes, including intellectual disability (ID). However, evidence addressing the role of neonatal thyroid hormone insufficiencies in the altered neurobiology underlying autism spectrum disorders (ASD), particularly among its subphenotypes, is limited. We conducted a population‐based, case–control study among a sample of children born during 2000–2003 in Southern California. We examined neonatal thyroid‐stimulating hormone (TSH) measured during routine newborn screening among children later diagnosed with ASD (n = 518) or ID (n = 145) and general population (GP) controls (n = 399). TSH was further analyzed in relation to ASD subgroups of intellectual ability and onset type (early‐onset ASD vs. ASD with regression) ascertained by expert review of developmental services records. Odds ratios (ORs) of the differences in TSH between groups were obtained from multivariate logistic regression. We examined neonatal TSH as continuous (ln‐transformed) and as quartiles. We found no association between continuous neonatal TSH levels and ASD (adj‐OR: 1.00, 95% CI: 0.79–1.26) nor ID (adj‐OR = 1.01, 95% CI: 0.73–1.40). Among ASD subphenotypes, we observed a suggestive inverse trend between ASD with regression and TSH, though the association only reached statistical significance in the highest TSH quartile (adj‐OR: 0.50, 95% CI: 0.26–0.98). While there was little evidence that neonatal TSH is related to overall ASD risk, more work is needed to understand the influence of thyroid hormones on ASD subphenotypes. Autism Res 2020, 13: 444–455. © 2019 International Society for Autism Research,Wiley Periodicals, Inc.Lay SummaryLow levels of thyroid hormone at birth can negatively impact brain development. We studied whether newborn levels of thyroid stimulating hormone (TSH) were associated with autism spectrum disorder (ASD) and its subtypes in a sample of children born in California. Newborn TSH was not related to the overall risk of ASD or intellectual disability. However, the relationships of thyroid hormone levels at birth and specific subtypes of ASD, particularly ASD with developmental regression, may need more research.
Fermentation of hemicellulose liquor from Brewer's spent grain using Scheffersomyces stipitis and Pachysolen tannophilus for production of 2G ethanol and xylitol
Authors: da Silva Elizabeth G. , Borges Alex S. , Maione Nicole R. , Castiglioni Gabriel L. , Suarez Carlos A. G. , Montano Inti D. C. 
Published: December 2019

AbstractBeer production generates brewer's spent grain as a byproduct. This biomass contains lignin, cellulose, and hemicellulose, and can be used for the production of second‐generation (2G) ethanol and xylitol. For this to be economically viable, fermentable fractions must be used, allowing the conversion of cellulose and hemicellulose to ethanol. This study evaluated the fermentation of hemicellulose liquor from brewer's spent grain (HLBS) in aerobic and oxygen‐ limited conditions using Scheffersomyces stipitis and Pachysolen tannophilus. Results were compared with data obtained in a complex medium (YPX) and a minimal medium (MMX). In aerobic conditions, for S. stipitis in the HLBS medium, μ
max = 0.12 h−1, Y
ethanol/xylose = 0.14 and selectivity for ethanol over xylitol (S
ethanol/xylitol) 3.4 gethanol g−1
xylitol were obtained. Under oxygen‐limited conditions, Y
ethanol/xylose = 0.22 and S
ethanol/xylitol = 1.17 gethanol g−1
xylitol were obtained. For P. tannophilus, under aerobic conditions, the HLBS medium gave μ
max = 0.08 h−1, and Y
ethanol/xylose = 0.005, with selectivity for ethanol over xylitol (S
ethanol/xylitol) of 0.12 gethanol g−1
xylitol. In oxygen‐limited conditions, Y
ethanol/xylose = 0.09 and S
ethanol/xylitol = 0.20 gethanol g−1
xylitol were obtained. This is because the metabolism of these aerobic yeasts directs the carbon flow to cell growth, while with oxygen limitation it is directed to metabolite production. The HLBS medium was promising for production in the context of a biorefinery. When comparing the two yeasts, S. stipitis presented better ethanol production and P. tannophilus better xylitol production under the conditions that were studied. © 2019 Society of Chemical Industry and John Wiley & Sons, Ltd
PBX‐WNT‐P63‐IRF6pathway in nonsyndromic cleft lip and palate
Authors: Maili Lorena , Letra Ariadne , Silva Renato , Buchanan Edward P. , Mulliken John B. , Greives Matthew R. , Teichgraeber John F. , Blackwell Steven J. , Ummer Rohit , Weber Ryan , Chiquet Brett , Blanton Susan H. , Hecht Jacqueline T. 
Published: December 2019

AbstractNonsyndromic cleft lip and palate (NSCLP) is one of the most common craniofacial anomalies in humans, affecting more than 135,000 newborns worldwide. NSCLP has a multifactorial etiology with more than 50 genes postulated to play an etiologic role. The genetic pathway comprised ofPbx‐Wnt‐p63‐Irf6genes was shown to control facial morphogenesis in mice and proposed as a regulatory pathway for NSCLP. Based on these findings, we investigated whether variation inPBX1,PBX2, andTP63, and their proposed interactions were associated with NSCLP. Fourteen single nucleotide variants (SNVs) in/nearbyPBX1,PBX2, andTP63were genotyped in 780 NSCLP families of nonHispanic white (NHW) and Hispanic ethnicities. Family‐based association tests were performed for individual SNVs stratified by ethnicity and family history of NSCLP. Gene–gene interactions were also tested. A significant association was found forPBX2rs3131300 and NSCLP in combined Hispanic families (p= .003) while nominal association was found forTP63rs9332461 in multiplex Hispanic families (p= .005). Significant haplotype associations were observed forPBX2in NHW (p= .0002) and Hispanic families (p= .003), and forTP63in multiplex Hispanic families (.003). An independent case–control group was used to validate findings, and significant associations were found withPBX1rs6426870 (p= .007) andTP63rs9332461 (p= .03). Gene–gene interactions were detected betweenPBX1/PBX2/TP63withIRF6in NHW families, and betweenPBX1withWNT9Bin both NHW and Hispanic families (p < .0018). This study provides the first evidence for a role ofPBX1andPBX2, additional evidence for the role ofTP63, and support for the proposedPBX‐WNT‐TP63‐IRF6regulatory pathway in the etiology of NSCLP.
Rapid analysis of Saposhnikovia divaricate decoction metabolism in rats by UHPLC–Q‐TOFMS and multivariate statistical analysis
Authors: Li Yueyue , Zhao Liang , Lv Diya , Wang Rong , Zhu Zhenyu , Yuan Yongfang 
Published: December 2019

AbstractSaposhnikovia divaricata is a commonly used traditional Chinese medicine in treating various diseases such as pyrexia, rheumatism and headache. So far, there have been few reports on the metabolism of orally administered Saposhnikovia divaricate decoction (SDD), hindering further study on its bioactive components and their pharmacological characteristics. In the present study, ultra‐performance liquid chromatography–quadrupole time‐of‐flight mass spectrometry (UHPLC–Q‐TOFMS) was used coupled with principal component analysis (PCA) and partial least squared discriminant analysis (PLS‐DA) to rapidly discover and identify the metabolites of SDD. According to the result of PLS‐DA, a total of 139 ions of interest including 87 positive ions and 52 negative ions were extracted as SDD‐related xenobiotics in urine. Finally, 12 and 65 compounds were identified as absorbed parent components and metabolites of SDD, respectively. Among them, 40 new metabolites were reported for the first time. Our results suggested that hydrolysis, hydroxylation, glucuronidation and sulfation are the major metabolic pathways of chromones, while hydroxylation, hydrogenation and sulfation are the main metabolic pathways of coumarins. This study is the first to explore the absorption and metabolism of SDD using UHPLC–Q‐TOFMS, with results providing a basis for further study of its pharmacokinetics and discovery of its bioactive components.
Effects of cysteine, asparagine, or glutamine limitations in Chinese hamster ovary cell batch and fed‐batch cultures
Authors: Ghaffari Navid , Jardon Mario A. , Krahn Natalie , Butler Michael , Kennard Malcolm , Turner Robin F. B. , Gopaluni Bhushan , Piret James M. 
Published: December 2019

AbstractAmino acid availability is a key factor that can be controlled to optimize the productivity of fed‐batch cultures. To study amino acid limitation effects, a serum‐free chemically defined basal medium was formulated to exclude the amino acids that became depleted in batch culture. The effect of limiting glutamine, asparagine, and cysteine on the cell growth, metabolism, antibody productivity, and product glycosylation was investigated in three Chinese hamster ovary (CHO) cell lines (CHO‐DXB11, CHO‐K1SV, and CHO‐S). Cysteine limitation was detrimental to both cell proliferation and productivity for all three CHO cell lines. Glutamine limitation reduced growth but not cell specific productivity, whereas asparagine limitation had no significant effect on either growth or cell specific productivity. Neither glutamine nor asparagine limitation significantly affected antibody glycosylation. Replenishing the CHO‐DXB11 culture with cysteine after 1 day of cysteine limitation allowed the cells to partially recover their growth and productivity. This recovery was not observed after 2 days of cysteine limitation. Based on these findings, a fed‐batch protocol was developed using single or mixed amino acid supplementation. Although cell density and antibody concentration were lower compared to a commercial feed, the feeds based on cysteine supplementation yielded comparable cell specific productivity. Overall, this study showed that different amino acid limitations have varied effects on the performance of CHO cell cultures and that maintaining cysteine availability is a critical process parameter for the three cell lines investigated.