bluuebunny/crossref_metadata_2025_split huggingface dataset:
Current Structural Knowledge on Cystathionine β‐Synthase, a Pivotal Enzyme in the Transsulfuration Pathway
Authors: González‐Recio Irene , Fernández‐Rodríguez Carmen , Simón Jorge , Goikoetxea‐Usandizaga Naroa , Martínez‐Chantar Maria Luz , Astegno Alessandra , Majtan Tomas , Martinez‐Cruz Luis Alfonso 
Published: October 2020

AbstractCystathionine β‐synthase (CBS), the first enzyme of the reverse transsulfuration pathway, catalyses the pyridoxal‐5′‐phosphate (PLP)‐dependent β‐replacement reaction that condensesl‐serine with L‐homocysteine to yield cystathionine and water. Besides this canonical reaction and using cysteine and homocysteine as substrates, CBS can also efficiently produce hydrogen sulfide (H2S) through alternative β‐replacement and β‐elimination processes. The structural information on the full‐length enzyme has remained elusive for decades and is still very scarce, but some advances in the recent years have uncovered its peculiar modular architecture, provided a glimpse of its conformational landscape and revealed some of the reaction intermediates formed during the catalysis. All these data have helped comprehend, at least partially, the regulatory mechanisms and the catalytic abilities of the enzyme across different organisms. This article aims to overview the current information on the CBS structure from its most sophisticated variants found in mammals to its simplest homologs in bacteria. A more detailed understanding of CBS structure and function is needed, which could subsequently serve as a basis for the development of drugs to treat human diseases, such as CBS‐deficient homocystinuria, Alzheimer diseases and some cancers, as well as of new antibiotics against multidrug‐resistant pathogenic bacteria.Key ConceptsReverse transsulfuration is a two‐step metabolic route that allows the conversion of the essential amino acid methionine into cysteine. This process generates hydrogen sulfide and impedes the accumulation of the toxic intermediate homocysteine.Hydrogen sulfide is an important gasotransmitter involved in physiological functions such as neuroprotection and the regulation of blood pressure.Homocystinuria consists of the abnormal accumulation of homocysteine, and is an inherited disorder due to the deficient activity of CBS. This pathology causes vascular thromboses, skeletal defects, mental retardation, and even early death.The three‐dimensional structure of CBS provides a suitable template to develop drugs to treat homocystinuria and related pathologies in humans.The comparative structural analysis of the CBS enzymes from different organisms are key to intervene in their sulfur metabolism, and thus represents a potential therapeutic approach against pathogens.
Cell‐Based Therapy for Canavan Disease Using Human iPSC‐Derived NPCs and OPCs
Authors: Feng Lizhao , Chao Jianfei , Tian E , Li Li , Ye Peng , Zhang Mi , Chen Xianwei , Cui Qi , Sun Guihua , Zhou Tao , Felix Gerardo , Qin Yue , Li Wendong , Meza Edward David , Klein Jeremy , Ghoda Lucy , Hu Weidong , Luo Yonglun , Dang Wei , Hsu David , Gold Joseph , Goldman Steven A. , Matalon Reuben , Shi Yanhong 
Published: October 2020

AbstractCanavan disease (CD) is a fatal leukodystrophy caused by mutation of the aspartoacylase (ASPA) gene, which leads to deficiency in ASPA activity, accumulation of the substrate N‐acetyl‐L‐aspartate (NAA), demyelination, and spongy degeneration of the brain. There is neither a cure nor a standard treatment for this disease. In this study, human induced pluripotent stem cell (iPSC)‐based cell therapy is developed for CD. A functionalASPAgene is introduced into patient iPSC‐derived neural progenitor cells (iNPCs) or oligodendrocyte progenitor cells (iOPCs) via lentiviral transduction or TALEN‐mediated genetic engineering to generate ASPA iNPC or ASPA iOPC. After stereotactic transplantation into a CD (Nur7) mouse model, the engrafted cells are able to rescue major pathological features of CD, including deficient ASPA activity, elevated NAA levels, extensive vacuolation, defective myelination, and motor function deficits, in a robust and sustainable manner. Moreover, the transplanted mice exhibit much prolonged survival. These genetically engineered patient iPSC‐derived cellular products are promising cell therapies for CD. This study has the potential to bring effective cell therapies, for the first time, to Canavan disease children who have no treatment options. The approach established in this study can also benefit many other children who have deadly genetic diseases that have no cure.
An Unexpected Split‐Merge Pathway in the Assembly of the Symmetric Nonribosomal Peptide Antibiotic Closthioamide
Authors: Dunbar Kyle L. , Dell Maria , Molloy Evelyn M. , Büttner Hannah , Kumpfmüller Jana , Hertweck Christian 
Published: October 2020

AbstractClosthioamide (CTA) is a symmetric nonribosomal peptide (NRP) comprised of two diaminopropane‐linked polythioamidated monomers. CTA is biosynthesized by Ruminiclostridium cellulolyticum via an atypical NRP synthetase (NRPS)‐independent biosynthetic pathway. Although the logic for monomer assembly was recently elucidated, the strategy for the biosynthesis and incorporation of the diamine linker remained a mystery. By means of genome editing, synthesis, and in vitro biochemical assays, we demonstrate that the final steps in CTA maturation proceed through a surprising split‐merge pathway involving the dual use of a thiotemplated intermediate. This pathway includes the first examples of an aldo‐keto reductase catalyzing the reductive release of a thiotemplated product, and of a transthioamidating transglutaminase. In addition to clarifying the remaining steps in CTA assembly, our data shed light on largely unexplored pathways for NRPS‐independent peptide biosynthesis.
Supramolecular Chirogenesis Induced by Platinum(II) Tweezers with Excellent Environmental Tolerance
Authors: Liu Mingyang , Han Yifei , Zhong Hua , Zhang Xiaolong , Wang Feng 
Published: October 2020

AbstractSupramolecular chirogenesis has emerged as an effective strategy to access symmetry breaking in artificial systems. However, the chirogenic signals suffer from high susceptibility toward environmental variations. An effective strategy has been developed to address this issue by constructing platinum(II)‐based tweezer/guest complexes stabilized by two‐fold donor–acceptor and PtII–PtII metal–metal interactions. Upon guest encapsulation, the two pincers on the achiral PtII tweezer undergo a stereospecific twist to minimize steric repulsion, thus locking tweezer/guest complexes into the preferred chiral conformations. The induced chiroptical effects display outstanding solvent and temperature tolerance, ascribed to the balance between electrostatic and desolvation effects for the involved non‐covalent interactions. Moreover, hierarchical and multi‐component supramolecular assembly of tweezer/guest complexes provide a convenient way to modulate chirogeneic signals for their intensities.
Molecular Chemiluminescent Probes with a Very Long Near‐Infrared Emission Wavelength for in Vivo Imaging
Authors: Huang Jingsheng , Jiang Yuyan , Li Jingchao , Huang Jiaguo , Pu Kanyi 
Published: October 2020

AbstractChemiluminescence imaging is imperative for diagnostics and imaging due to its intrinsically high sensitivity. To improve in vivo detection of biomarkers, chemiluminophores that simultaneously possess near‐infrared (NIR) emission and modular structures amenable to construction of activatable probes are highly desired; however, these are rare. Herein, we report two chemiluminophores with record long NIR emission (>750 nm) via integration of dicyanomethylene‐4H‐benzothiopyran or dicyanomethylene‐4H‐benzoselenopyran with dioxetane unit. Caging of the chemiluminophores with different cleavable moieties produces NIR chemiluminescence probes (NCPs) that only produce signals upon reaction with reactive oxygen species or enzymes, for example, β‐galactosidase, with a tissue‐penetration depth of up to 2 cm. Thus, this study provides NIR chemiluminescence molecular scaffolds applicable for in vivo turn‐on imaging of versatile biomarkers in deep tissues.
Proton Nuclear Magnetic Resonance‐Based Method for the Quantification of Epoxidized Methyl Oleate
Authors: Kaur Avneet , Bhardwaj Neha , Kaur Amanpreet , Abida Km , Nagaraja Tejo Prakash , Ali Amjad , Prakash Ranjana 
Published: October 2020

AbstractEpoxidized methyl esters (EMO) with their high oxirane ring reactivity, acts as a raw material in the synthesis of various industrial chemicals including polymers, stabilizers, plasticizers, glycols, polyols, carbonyl compounds, biolubricants etc. EMO has been generally quantified by the gas chromatography (GC) and high‐performance liquid chromatography (HPLC) techniques. Taking into the account of the limitations of these techniques, two qHNMR‐based equations have been proposed for the quantification of EMO in the mixture of EMO and methylesters (MO). The validity of the proposed method was determined using standard mixtures of MO and EMO having different molar concentrations. The developed equations have been applied on the samples of EMO prepared from oleic acid in two‐step process viz., esterification followed by epoxidation. The qHNMR‐based EMO quantification showed acceptable agreement with the results obtained from HPLC analysis.
Zu den Ursachen und zur Vermeidung von Schlosssprengungen bei kombinierten Spundwänden
Authors: Osthoff David 
Published: October 2020

AbstractKombinierte Spundwände aus Trag‐ und Zwischenbohlen sind eine langjährig bewährte Lösung und werden dann eingesetzt, wenn die Tragfähigkeit oder die Steifigkeit von Wellenspundwänden nicht mehr ausreicht. Die Verbindung zwischen Trag‐ und Zwischenbohlen erfolgt über die Spundwandschlösser. Während des Einbringens der Zwischenbohlen kann es zu einem Herauslaufen oder einem Blockieren des verbindenden Spundwandschlosses kommen. Diese sog. Schlosssprengungen sind umgehend zu sanieren, um Erosion des anstehenden Bodens und somit Versackungen hinter der Wand zu verhindern. Im folgenden Beitrag werden mögliche Ursachen für Schlosssprengungen aufgeführt und evaluiert. Die Untersuchungen umfassen neben einer Fallstudie zu ausgeführten kombinierten Spundwänden Labor‐ und Feldversuche, die in Verbindung mit Finite‐Elemente‐Berechnungen die mechanischen und mechanisch‐thermischen Prozesse im Schloss während der Einbringung betrachten. Zur Vermeidung von Schlosssprengungen bei kombinierten Spundwänden werden Lösungsaspekte im Rahmen der Planung, der Herstellung und der Ausführung vorgestellt. Dies erfolgt in Ergänzung zu den bestehenden Empfehlungen des Arbeitsausschusses Ufereinfassungen (EAU).
Tissue‐disruption‐induced cellular stochasticity and epigenetic drift: Common origins of aging and cancer?
Authors: Capp Jean‐Pascal , Thomas Frédéric 
Published: October 2020

AbstractAge‐related and cancer‐related epigenomic modifications have been associated with enhanced cell‐to‐cell gene expression variability that characterizes increased cellular stochasticity. Since gene expression variability appears to be highly reduced by—and epigenetic and phenotypic stability acquired through—direct or long‐range cellular interactions during cell differentiation, we propose a common origin for aging and cancer in the failure to control cellular stochasticity by cell–cell interactions. Tissue‐disruption‐induced cellular stochasticity associated with epigenetic drift would be at the origin of organ dysfunction because of an increase in phenotypic variation among cells, ultimately leading to cell death and organ failure through a loss of coordination in cellular functions, and eventually to cancerization. We propose mechanistic research perspectives to corroborate this hypothesis and explore its evolutionary consequences, highlighting a positive correlation between the median age of mass loss onset (a proxy for the onset of organ aging) and the median age at cancer diagnosis.
Prognostic impact of collaterals in patients with a coronary chronic total occlusion: A meta‐analysis of over 3,000 patients
Authors: Allahwala Usaid K. , Nour Daniel , Bhatia Kunwardeep , Ward Michael R. , Lo Sidney , Weaver James C. , Bhindi Ravinay 
Published: October 2020

AbstractObjectivesTo assess the prognostic implications of the degree of coronary collaterals on outcomes in patients with a CTO.BackgroundCoronary chronic total occlusions (CTO) are identified frequently in patients undergoing coronary angiography and have been associated with poorer prognosis. Whether the degree of coronary collaterals, the hallmark of CTOs impacts prognosis, is unknown.MethodsA search of EMBASE, MEDLINE, and Cochrane Library was conducted to identify studies reporting on coronary collaterals and risk of all‐cause mortality, acute myocardial infarction (AMI) and successful percutaneous coronary intervention (PCI). Patients with Rentrop grade 0 or 1 collaterals were defined as poor collaterals, while Rentrop grade 2 or 3 were defined as robust collaterals.ResultsTwelve studies with a total of 3,369 were included. Patients with robust collaterals did not have lower rates of AMI (OR: 0.89, 95%CI: 0.39–2.04) or lower rates of all‐cause mortality (OR: 0.81, 95% CI: 0.42–1.58), however were more likely to have successful PCI (OR: 4.04, 95%CI: 1.10–14.85).ConclusionThe presence of robust collaterals is not associated with lower rates of AMI or mortality, but does increase the likelihood of successful CTO PCI. These results have importance implications with respect to the indications for CTO PCI as well as selecting appropriate patients to undergo the procedure.
Elucidating the Promotional Effect of Cerium in the Dry Reforming of Methane
Authors: Rodriguez‐Gomez Alberto , Lopez‐Martin Angeles , Ramirez Adrian , Gascon Jorge , Caballero Alfonso 
Published: October 2020

AbstractA series of Ni‐Ce catalysts supported on SBA‐15 has been prepared by co‐impregnation, extensively characterized and evaluated in the carbon dioxide reforming of methane (DRM). The characterization by TEM, XRD and TPR has allowed us to determine the effect of metal loading on metal dispersion. Cerium was found to improve nickel location inside the mesopores of SBA‐15 and to suppress coke formation during the DRM reaction. The analysis by XPS allowed us to associate the high cerium dispersion with the presence of low‐coordinated Ce3+ sites, being main responsible for its promotional effect. A combination of XAS and XPS has permitted us to determine the physicochemical properties of metals under reduction conditions. The low nickel coordination number determined by XAS in N‐Ce doped systems after reduction suggests the generation of very small nickel particles which showed greater catalytic activity and stability in the reaction, and a remarkable resistance to coke formation.
Stability of Cobalt Particles In and Outside HZSM‐5 under CO Hydrogenation Conditions Studied by ex situ and in situ Electron Microscopy
Authors: Straß‐Eifert Angela , Sheppard Thomas L. , Damsgaard Christian D. , Grunwaldt Jan‐Dierk , Güttel Robert 
Published: October 2020

AbstractDesigning stable materials for processes operating under harsh reaction conditions, like CO hydrogenation, is a challenging topic in catalysis. These may provoke several deactivation mechanisms simultaneously, like thermal sintering, oxidation or poisoning of the active sites. We report HZSM‐5 supported cobalt catalysts, exhibiting cobalt nanoparticles encapsulated inside, or located at the exterior of the ZSM‐5 support. The materials were studied by a combination of ex situ and in situ electron microscopy with respect to the growth of the cobalt particles. After 1200 h time on stream under CO hydrogenation conditions, the spent catalyst showed minimal sintering of encapsulated cobalt particles. In situ environmental TEM experiments under model reduction and CO hydrogenation conditions indicate the presence of cobalt nanoparticles, which appear highly resistant towards sintering even up to 700 °C. These results provide a first indication for the preparation of sinter stable catalysts suitable for operating in harsh reaction environments.
Financial planning: A research agenda for the next decade
Authors: Bogan Vicki L. , Geczy Christopher C. , Grable John E. 
Published: October 2020

AbstractWe provide an informed discussion about challenges, opportunities and the future of research and practice in the field of financial planning over the next 10 years. As editors of Financial Planning Review, using a mix‐methods approach and a survey of subject‐matter expert views, we outline what we believe are some of the future key themes of financial planning. We also present an overview of the challenges and opportunities facing researchers who are working to build, inform, and expand the financial planning body of literature. Further, we discuss the financial planning‐related topics that would benefit most from increased research and study.
In Situ Mass Spectrometric and Kinetic Investigations of Soai's Asymmetric Autocatalysis
Authors: Trapp Oliver , Lamour Saskia , Maier Frank , Siegle Alexander F. , Zawatzky Kerstin , Straub Bernd F. 
Published: October 2020

AbstractInvited for the cover of this issue is Oliver Trapp and his co‐workers at Ludwig‐Maximilians‐Universität München, the Max‐Planck‐Institute for Astronomy and Ruprecht‐Karls‐Universität Heidelberg. The image depicts a magic trick representing the autocatalytic process reported in the manuscript. Read the full text of the article at 10.1002/chem.202003260.
Green‐, Red‐, and Infrared‐Emitting Polymorphs of Sterically Hindered Push–Pull Substituted Stilbenes
Authors: Pauk Karel , Luňák Stanislav , Růžička Aleš , Marková Aneta , Mausová Anna , Kratochvíl Matouš , Melánová Klára , Weiter Martin , Imramovský Aleš , Vala Martin 
Published: October 2020

AbstractThe synthesis, XRD single‐crystal structure, powder XRD, and solid‐state fluorescence of two new DPA‐DPS‐EWG derivatives (DPA=diphenylamino, DPS=2,5‐diphenyl‐stilbene, EWG=electron‐withdrawing group, that is, carbaldehyde or dicyanovinylene, DCV) are described. Absorption and fluorescence maxima in solvents of various polarity show bathochromic shifts with respect to the parent DPA‐stilbene‐EWGs. The electronic coupling in dimers and potential twist elasticity of monomers were studied by density functional theory. Both polymorphs of the CHO derivative emit green fluorescence (527 and 550 nm) of moderate intensity (10 % and 5 %) in polycrystalline powder form. Moderate (5 %) red (672 nm) monomer‐like emission was also observed for the first polymorph of the DCV derivative, whereas more intense (32 %) infrared (733 nm) emission of the second polymorph was ascribed to the excimer fluorescence.
The costs of treating and not treating patients with chronic myeloid leukemia with tyrosine kinase inhibitors among Medicare patients in the United States
Authors: Seymour Erlene K. , Ruterbusch Julie J. , Winn Aaron N. , George Julie A. , Beebe‐Dimmer Jennifer L. , Schiffer Charles A. 
Published: October 2020

BackgroundPatients with high cost‐sharing of tyrosine kinase inhibitors (TKIs) experience delays in treatment for chronic myeloid leukemia (CML). To the authors' knowledge, the clinical outcomes among and costs for patients not receiving TKIs are not well defined.MethodsUsing the Surveillance, Epidemiology, and End Results (SEER)–Medicare database, the authors evaluated differences in TKI initiation, health care use, cost, and survival among patients with CML with continuous Medicare Parts A and B and Part D coverage who were diagnosed between 2007 and 2015.ResultsA total of 941 patients were included. Approximately 29% of all patients did not initiate treatment with TKIs within 6 months (non‐TKI users), and had lower rates of BCR‐ABL testing and more hospitalizations compared with TKI users. Approximately 21% were not found to have any TKI claims at any time. TKI initiation rates within 6 months of diagnosis increased for all patients over time (61% to 85%), with greater improvements observed in patients receiving subsidies (55% to 90%). Total Medicare costs were greater in patients treated with TKIs, with approximately 50% because of TKI costs. Non‐TKI users had more inpatient costs compared with TKI users. Trends in cost remained significant when adjusting for age and comorbidities. The median overall survival was 40 months (95% confidence interval [95% CI], 34‐48 months) compared with 86 months (95% CI, 73 months to not reached), respectively, for non‐TKI users versus TKI users, a finding that remained consistent when adjusting for age, comorbidities, and subsidy status (hazard ratio, 2.23; 95% CI, 1.77‐2.81).ConclusionsApproximately 21% of all patients with CML did not receive TKIs at any time. Cost‐sharing subsidies consistently are found to be associated with higher initiation rates. Non‐TKI users had higher inpatient costs and poorer survival outcomes. Interventions to lower TKI costs for all patients are desirable.
Levels and variables associated with psychological distress during confinement due to the coronavirus pandemic in a community sample of Spanish adults
Authors: Pérez Sandra , Masegoso Andrea , Hernández‐Espeso Nazaret 
Published: October 2020

AbstractDue to the COVID‐19 pandemic's consequences and the state of alarm, literature has shown that people worldwide have experienced severe stressors that have been associated with increased prevalence of emotional distress. In this study, we explored psychological distress (depression, anxiety, and somatization symptoms) using an online survey platform in a sample of 1,781 Spanish adults during the confinement due to COVID‐19, relationships between distress and sleep problems, affect, pain, sleep, emotional regulation, gender, type of housing, history of psychopathology, and living alone during the confinement, and differences depending on demographic and psychological variables. Results showed that between 25% and 39% of the sample referred to clinically significant levels of distress. In addition, women showed higher levels of distress, negative affect, perception of pain, and cognitive reappraisal and lower levels of emotional suppression and sleep quality than men. A history of psychopathology, being younger, living alone or in a flat was associated with higher distress. Finally, the variables most strongly related to distress were negative and positive affect, levels of pain, sleep quality, and emotional suppression. Our results highlight the important role of emotional suppression, cognitive reappraisal, and loneliness and the impact of being a woman and younger in Spain during the COVID‐19 pandemic. Therefore, it would be necessary to provide assessments of distress levels in these population groups and focus psychological preventive and therapeutic online interventions on expressing emotions and preventing loneliness.