bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design, Synthesis, Radiosynthesis and Biological Evaluation of Fenretinide Analogues as Anticancer and Metabolic Syndrome‐Preventive Agents
Authors: Patruno Ilaria , Thompson Dawn , Dall'Angelo Sergio , Windhorst Albert D. , Vugts Danielle J. , Poot Alex J. , Mody Nimesh , Zanda Matteo 
Published: June 2020

AbstractFenretinide (4‐HPR) is a synthetic derivative of all‐trans‐retinoic acid (ATRA) characterised by improved therapeutic properties and toxicological profile relative to ATRA. 4‐HPR has been mostly investigated as an anti‐cancer agent, but recent studies showed its promising therapeutic potential for preventing metabolic syndrome. Several biological targets are involved in 4‐HPR's activity, leading to the potential use of this molecule for treating different pathologies. However, although 4‐HPR displays quite well‐understood multitarget promiscuity with regards to pharmacology, interpreting its precise physiological role remains challenging. In addition, despite promising results in vitro, the clinical efficacy of 4‐HPR as a chemotherapeutic agent has not been satisfactory so far. Herein, we describe the preparation of a library of 4‐HPR analogues, followed by the biological evaluation of their anti‐cancer and anti‐obesity/diabetic properties. The click‐type analogue 3 b showed good capacity to reduce the amount of lipid accumulation in 3T3‐L1 adipocytes during differentiation. Furthermore, it showed an IC50 of 0.53±0.8 μM in cell viability tests on breast cancer cell line MCF‐7, together with a good selectivity (SI=121) over noncancerous HEK293 cells. Thus, 3 b was selected as a potential PET tracer to study retinoids in vivo, and the radiosynthesis of [18F]3b was successfully developed. Unfortunately, the stability of [18F]3b turned out to be insufficient to pursue imaging studies.
Delicate Balance of Non‐Covalent Forces Govern the Biocompatibility of Graphitic Carbon Nitride towards Genetic Materials
Authors: Mukhopadhyay Titas Kumar , Datta Ayan 
Published: June 2020

AbstractDespite a plethora of suggested technological and biomedical applications, the nanotoxicity of two‐dimensional (2D) graphitic carbon nitride (g‐C3N4) towards biomolecules remains elusive. To address this issue, we employ all‐atom classical molecular dynamics simulations and investigate the interactions between nucleic acids and g‐C3N4. It is revealed that, toxicity is modulated through a subtle balance between electrostatic and van der Waals interactions. When the exposed nucleobases interact through predominantly short‐ranged van der Waals and π–π stacking interactions, they get deviated from their native disposition and adsorb on the surface, leading to loss of self‐stacking and intra‐quartet H‐bonding along with partial disruption of the native structure. In contrast, for the interaction with double‐stranded structures of both DNA and RNA, long‐range electrostatics govern the adsorption phenomena since the constituent nucleobases are relatively concealed and wrapped, thereby resulting in almost complete preservation of the nucleic acid structures. Construction of free energy landscapes for lateral translation of adsorbed nucleic acids suggests decent targeting specificity owing to their restricted movement on g‐C3N4. The release times of nucleic acids adsorbed through predominant electrostatics are significantly less than those adsorbed through stacking with the surface. It is therefore proposed that g‐C3N4 would induce toxicity towards any biomolecule having bare residues available for strong van der Waals and π–π stacking interactions relative to those predominantly interacting through electrostatics.
Through‐Space Polar‐π Interactions in 2,6‐Diarylthiophenols
Authors: Jian Jie , Poater Jordi , Hammink Roel , Tinnemans Paul , McKenzie Christine J. , Bickelhaupt F. Matthias , Mecinović Jasmin 
Published: June 2020

AbstractThe front cover artwork is provided by Marijn Maas from the group of Prof. Jasmin Mecinović (University of Southern Denmark). The image shows the stabilization of thiols by aromatic rings, as a result of energetically favorable SH‐π interactions in a designed small molecule and in proteins. Read the full text of the Article at 10.1002/cphc.202000132.
Two Equivalent Internal Rotations in the Microwave Spectrum of 2,6‐Dimethylfluorobenzene
Authors: Khemissi Safa , Nguyen Ha Vinh Lam 
Published: June 2020

AbstractLarge amplitude motion of methyl groups in isolated molecules is a fundamental phenomenon in molecular physics. The methyl torsional barrier is sensitive to the steric and electronic environment in the surrounding of the methyl group, making the methyl group a detector of the molecular structure. To probe this eﬀect, the microwave spectrum of 2,6‐dimethylfluorobenzene, one of the six isomers of dimethylfluorobenzene, was measured using two pulsed molecular jet Fourier transform microwave spectrometers operating in the frequency range from 2 to 40 GHz. Due to internal rotations of two equivalent methyl groups with relatively low torsional barriers, all rotational transitions split into quartets with separations of up to several hundreds of MHz. The splittings were analyzed and modeled to deduce a torsional barrier of 236.7922 (21) cm−1. The results are compared to those obtained from quantum chemical calculations and with other fluorine substituted toluene derivatives of the current literature where the methyl group is adjacent to a fluorine atom.
High‐Pressure‐Mediated Thiourea‐Organocatalyzed Asymmetric Michael Addition to (Hetero)aromatic Nitroolefins: Prediction of Reaction Parameters by PCP‐SAFT Modelling
Authors: Weinbender Thomas , Knierbein Michael , Bittorf Lukas , Held Christoph , Siewert Riko , Verevkin Sergey P. , Sadowski Gabriele , Reiser Oliver 
Published: June 2020

AbstractThiourea‐organocatalyzed Michael additions of diethyl malonate to various heteroaromatic nitroolefins (13 examples) have been studied under high‐pressure (up to 800 MPa) and ambient pressure conditions. High pressure was conducive to enhanced product yields by a factor of 2–12 at a given reaction time, high reaction rates (reaction times were decreased from 72–24 h down to 4–24 h) and high enantioselectivity. Elucidating the effects of solvents for maximizing reaction rates and yields has been carried out using the Perturbed‐Chain Polar Statistical Associating Fluid Theory (PCP‐SAFT), allowing for the first time a prediction of the kinetic profiles under high‐hydrostatic‐pressure conditions.
Fundamentals of Microscopy
Authors: Sanderson Jeremy 
Published: June 2020

AbstractThe light (or optical) microscope is the icon of science. The aphorism “seeing is believing” is often quoted in scientific papers involving microscopy. Unlike many scientific instruments, the light microscope will deliver an image however badly it is set up. Fluorescence microscopy is a widely used research tool across all disciplines of biological and biomedical science. Most universities and research institutions have microscopes, including confocal microscopes. This introductory paper in a series detailing advanced light microscopy techniques explains the foundations of both electron and light microscopy for biologists and life scientists working with the mouse. An explanation is given of how an image is formed. A description is given of how to set up a light microscope, whether it be a brightfield light microscope on the laboratory bench, a widefield fluorescence microscope, or a confocal microscope. These explanations are accompanied by operational protocols. A full explanation on how to set up and adjust a microscope according to the principles of Köhler illumination is given. The importance of Nyquist sampling is discussed. Guidelines are given on how to choose the best microscope to image the particular sample or slide preparation that you are working with. These are the basic principles of microscopy that a researcher must have an understanding of when operating core bioimaging facility instruments, in order to collect high‐quality images. © 2020 Wiley Periodicals LLC.Basic Protocol 1: Setting up Köhler illumination for a brightfield microscopeBasic Protocol 2: Aligning the fluorescence bulb and setting up Köhler illumination for a widefield fluorescence microscopeBasic Protocol 3: Generic protocol for operating a confocal microscope
Self‐Assembled Quadruplex‐Inspired Peptide Nucleic Acid Tetramer for Artificial Photosynthesis
Authors: Basavalingappa Vasantha , Xue Bin , Rencus‐Lazar Sigal , Wang Wei , Tao Kai , Cao Yi , Gazit Ehud 
Published: June 2020

AbstractArtificial photosynthesis serves as a promising approach to exploit inexhaustible sunlight energy by converting it into chemical energy. However, the limited availability of stable systems with precise and coordinated organization of both an energy harvesting and a catalytic moiety hinders its practical application. Herein, for the first time, we demonstrate the utilization of self‐assembled G‐quadruplex inspired peptide nucleic acid (PNA)‐tetramer (Fmoc‐G‐PNA tetramer) as a template for an artificial photosynthesis system. Our approach involves integrating a ruthenium light harvesting antenna and a platinum catalyst on the Fmoc‐G‐PNA tetramer. In the presence of the Fmoc‐G‐PNA tetramer, a 3‐fold increase in the rate of NAD+ reduction to NADH is observed, compared to bare ruthenium complex and catalyst. Also, due to direct electron transfer, no external mediators are necessary, and the catalytic system is recyclable. This newly designed, easily fabricated Fmoc‐G‐PNA tetramer architecture could be a promising candidate for the design of bioinspired light harvesting systems and photoelectric devices.
Unravelling the Mechanism of Rechargeable Aqueous Zn–MnO2 Batteries: Implementation of Charging Process by Electrodeposition of MnO2
Authors: Yang Jie , Cao Jianyun , Peng Yudong , Yang Wenji , Barg Suelen , Liu Zhu , Kinloch Ian A. , Bissett Mark A. , Dryfe Robert A. W. 
Published: June 2020

AbstractPoor cycling stability and mechanistic controversies have hindered the wider application of rechargeable aqueous Zn–MnO2 batteries. Herein, direct evidence was provided of the importance of Mn2+ in this type of battery by using a bespoke cell. Without pre‐addition of Mn2+, the cell exhibited an abnormal discharge–charge profile, meaning it functioned as a primary battery. By adjusting the Mn2+ content in the electrolyte, the cell recovered its charging ability through electrodeposition of MnO2. Additionally, a dynamic pH variation was observed during the discharge–charge process, with a precipitation of Zn4(OH)6(SO4)⋅5H2O buffering the pH of the electrolyte. Contrary to the conventional Zn2+ intercalation mechanism, MnO2 was first converted into MnOOH, which reverted to MnO2 through disproportionation, resulting in the dissolution of Mn2+. The charging process occurred by the electrodeposition of MnO2, thus improving the reversibility through the availability of Mn2+ ions in the solution.
Contemporary human papillomavirus genotyping and correlations to peniscopy, cytology, and histopatology on over 1000 males
Authors: Truzzi Jose Carlos , da Silva Ismael Dale , Freire Marcos Paulo , Neto Miguel Jorge , Rodrigues Fabio Ferro , Maciel Gustavo Arantes , Girardi Ruana , Bertolini Sissi , Reis Leonardo O. 
Published: June 2020

AbstractObjectivesTo explore male human papillomavirus (HPV) contemporary genotyping epidemiology and correlations to peniscopy, cytology, and histopatology.MethodsMedical records of patients who had been submitted to HPV infection screening with genotyping, peniscopy, cytology, and histopathology in a period of 2 years were reviewed. Frequency analysis and correlations between the diagnostic tools were established.ResultsGenotype of 1132 men resulted in 69.2% (784) positivity for HPV DNA, 78% classified as high risk of oncogenesis. Co‐infections occurred in 429 (54.7%) and the most frequently identified types were HPV‐6, HPV‐42, and HPV‐16, in 133 (17%), 94 (12%), and 86 (11%) patients, respectively. Positive/negative predictive values of peniscopy, cytology, and histopathology were 83/31%, 92/32%, and 87/33%, respectively. As a result, though significant, the correlations between genotype and non‐molecular tests were poor.ConclusionsIn the current contemporary representative male cohort, over two thirds are positive for human HPV DNA, 78% of high risk and with over half co‐infections. Though significant, its correlation with non‐molecular tests is poor and while the positive predictive values of peniscopy, cytology, and histopatology are between 83% and 92%, their negative predictive values are as low as 31% to 33%.
Mortality limits used in wind energy impact assessment underestimate impacts of wind farms on bird populations
Authors: Schippers Peter , Buij Ralph , Schotman Alex , Verboom Jana , van der Jeugd Henk , Jongejans Eelke 
Published: June 2020

Abstract

The consequences of bird mortality caused by collisions with wind turbines are increasingly receiving attention. So‐called acceptable mortality limits of populations, that is, those that assume that 1%–5% of additional mortality and the potential biological removal (PBR), provide seemingly clear‐cut methods for establishing the reduction in population viability.

We examine how the application of these commonly used mortality limits could affect populations of the Common Starling, Black‐tailed Godwit, Marsh Harrier, Eurasian Spoonbill, White Stork, Common Tern, and White‐tailed Eagle using stochastic density‐independent and density‐dependent Leslie matrix models.

Results show that population viability can be very sensitive to proportionally small increases in mortality. Rather than having a negligible effect, we found that a 1% additional mortality in postfledging cohorts of our studied populations resulted in a 2%–24% decrease in the population level after 10 years. Allowing a 5% mortality increase to existing mortality resulted in a 9%–77% reduction in the populations after 10 years.

When the PBR method is used in the density‐dependent simulations, the proportional change in the resulting growth rate and carrying capacity was species‐independent and largely determined by the recovery factor (Fr). When Fr = 1, a value typically used for robust populations, additional mortality resulted in a 50%–55% reduction in the equilibrium density and the resulting growth rate. When Fr = 0.1, used for threatened populations, the reduction in the equilibrium density and growth rate was about 5%.

Synthesis and applications. Our results show that by allowing a mortality increase from wind farm collisions according to both criteria, the population impacts of these collisions can still be severe. We propose a simple new method as an alternative that was able to estimate mortality impacts of age‐structured stochastic density‐dependent matrix models.
Genome‐wide adaptive evolution to underground stresses in subterranean mammals: Hypoxia adaption, immunity promotion, and sensory specialization
Authors: Jiang Mengwan , Shi Luye , Li Xiujuan , Dong Qianqian , Sun Hong , Du Yimeng , Zhang Yifeng , Shao Tian , Cheng Han , Chen Weihua , Wang Zhenlong 
Published: June 2020

AbstractLife underground has provided remarkable examples of adaptive evolution in subterranean mammals; however, genome‐wide adaptive evolution to underground stresses still needs further research. There are approximately 250 species of subterranean mammals across three suborders and six families. These species not only inhabit hypoxic and dark burrows but also exhibit evolved adaptation to hypoxia, cancer resistance, and specialized sensory systems, making them an excellent model of evolution. The adaptive evolution of subterranean mammals has attracted great attention and needs further study. In the present study, phylogenetic analysis of 5,853 single‐copy orthologous gene families of five subterranean mammals (Nannospalax galili, Heterocephalus glaber, Fukomys damarensis, Condylura cristata, and Chrysochloris asiatica) showed that they formed fou distinct clusters. This result is consistent with the traditional systematics of these species. Furthermore, comparison of the high‐quality genomes of these five subterranean mammalian species led to the identification of the genomic signatures of adaptive evolution. Our results show that the five subterranean mammalian did not share positively selected genes but had similar functional enrichment categories, including hypoxia tolerance, immunity promotion, and sensory specialization, which adapted to the environment of underground stresses. Moreover, variations in soil hardness, climate, and lifestyles have resulted in different molecular mechanisms of adaptation to the hypoxic environment and different degrees of visual degradation. These results provide insights into the genome‐wide adaptive evolution to underground stresses in subterranean mammals, with special focus on the characteristics of hypoxia adaption, immunity promotion, and sensory specialization response to the life underground.
Clinical predictors of all‐cause mortality in patients presenting to specialist heart failure clinic with raised NT‐proBNP and no heart failure
Authors: Garg Pankaj , Wood Steven , Swift Andrew J. , Fent Graham , Lewis Nigel , Rogers Dominic , Rothman Alexander , Charalampopoulos Athanasios , Al‐Mohammad Abdallah 
Published: June 2020

AbstractAimsClinical outcomes for patients suspected of having heart failure (HF) who do not meet the diagnostic criteria of any type of HF by echocardiography remain unknown. The aim of this study was to investigate the clinical predictors of all‐cause mortality in patients with suspected HF, a raised N‐terminal pro‐b‐type natriuretic peptide (NTproBNP) and who do not meet the diagnostic criteria of any type of HF by echocardiography.Methods and resultsRelevant data were taken from the Sheffield HEArt Failure (SHEAF) registry (222349P4). The inclusion criteria were presence of symptoms raising suspicion of HF, NTproBNP > 400 pg/mL, and preserved left ventricular function. Exclusion criteria were any type of HF by echocardiography. The outcome was defined as all‐cause mortality. Cox proportional‐hazards regression model was used to investigate the association between the survival time of patients and clinical variables; 1031 patients were identified with NTproBNP > 400 pg/mL but who did not have echocardiographic evidence of HF. All‐cause mortality was 21.5% (222 deaths) over the mean follow‐up (FU) period of 6 ± 2 years. NTproBNP was similar in patients who were alive or dead (P = 0.96). However, age (HR 1, P < 0.01), chronic kidney disease (CKD, HR 1.2, P < 0.01), chronic pulmonary obstructive disease (COPD, HR 1.6, P < 0.01), dementia (HR 5.9, P < 0.01), male gender (HR 1.4, P < 0.01), first‐degree atrioventricular block (HR 2.1, P < 0.01), left axis deviation (HR 1.6, P = 0.04), and diabetes (HR 1.4, P = 0.03) were associated with all‐cause mortality. In multivariate regression, age, gender, CKD stage, COPD, and dementia were independently associated with mortality. In patients with NTproBNP > 627 pg/mL, NYHA class predicted death (II, 19.6%; III, 27.4%; IV, 66.7%; P < 0.01).ConclusionsPatients with no HF on echocardiography but raised NTproBNP suffer excess mortality particularly in the presence of certain clinical variables. Age, male gender, worsening CKD stage, presence of COPD, and dementia are independently associated with all‐cause mortality in these patients. An NTproBNP > 627 pg/mL coupled with NYHA class could identify patients at greatest risk of death.
Subjective status and perceived legitimacy across countries
Authors: Brandt Mark J. , Kuppens Toon , Spears Russell , Andrighetto Luca , Autin Frederique , Babincak Peter , Badea Constantina , Bae Jaechang , Batruch Anatolia , Becker Julia C. , Bocian Konrad , Bodroža Bojana , Bourguignon David , Bukowski Marcin , Butera Fabrizio , Butler Sarah E. , Chryssochoou Xenia , Conway Paul , Crawford Jarret T. , Croizet Jean‐Claude , de Lemus Soledad , Degner Juliane , Dragon Piotr , Durante Federica , Easterbrook Matthew J. , Essien Iniobong , Forgas Joseph P. , González Roberto , Graf Sylvie , Halama Peter , Han Gyuseog , Hong Ryan Y , Houdek Petr , Igou Eric R. , Inbar Yoel , Jetten Jolanda , Jimenez Leal William , Jiménez‐Moya Gloria , Karunagharan Jaya Kumar , Kende Anna , Korzh Maria , Laham Simon M. , Lammers Joris , Lim Li , Manstead Antony S. R. , Međedović Janko , Melton Zachary J. , Motyl Matt , Ntani Spyridoula , Owuamalam Chuma Kevin , Peker Müjde , Platow Michael J. , Prims J. P. , Reyna Christine , Rubin Mark , Saab Rim , Sankaran Sindhuja , Shepherd Lee , Sibley Chris G. , Sobkow Agata , Spruyt Bram , Stroebaek Pernille , Sümer Nebi , Sweetman Joseph , Teixeira Catia P. , Toma Claudia , Ujhelyi Adrienn , van der Toorn Jojanneke , van Hiel Alain , Vásquez‐Echeverría Alejandro , Vazquez Alexandra , Vianello Michelangelo , Vranka Marek , Yzerbyt Vincent , Zimmerman Jennifer L. 
Published: June 2020

AbstractThe relationships between subjective status and perceived legitimacy are important for understanding the extent to which people with low status are complicit in their oppression. We use novel data from 66 samples and 30 countries (N = 12,788) and find that people with higher status see the social system as more legitimate than those with lower status, but there is variation across people and countries. The association between subjective status and perceived legitimacy was never negative at any levels of eight moderator variables, although the positive association was sometimes reduced. Although not always consistent with hypotheses, group identification, self‐esteem, and beliefs in social mobility were all associated with perceived legitimacy among people who have low subjective status. These findings enrich our understanding of the relationship between social status and legitimacy.
Add‐on cannabidiol significantly decreases seizures in 3 patients with SYNGAP1 developmental and epileptic encephalopathy
Authors: Kuchenbuch Mathieu , D'Onofrio Gianluca , Chemaly Nicole , Barcia Giulia , Teng Théo , Nabbout Rima 
Published: June 2020

AbstractMutations in SYNGAP1 are associated with developmental delay, epilepsy, and autism spectrum disorder (ASD). Epilepsy is often drug‐resistant in this syndrome with frequent drop attacks. In a prospective study of add‐on cannabidiol (CBD), we identified three patients with SYNGAP1 mutations: two boys and one girl. Seizure onset was at 3.5, 8, and 18 months (M), respectively, with numerous atypical absences per day associated with eyelid myoclonia (2/3 patients), upper limb myoclonic jerks (2/3 patients), and drop attacks (all patients). Seizures were resistant to at least 5 antiepileptic drugs (AEDs). After CBD introduction, two patients were responders since M2 and achieve a seizure reduction of 90% and 80%, respectively, at M9 with disappearance of drop attacks. EEGs showed an improvement regarding background activity and interictal anomalies. The last patient showed a late response at M7 of treatment with an 80% decrease in seizure frequency. Caregiver in all three evaluated as much improved the status of their children. Treatment was well‐tolerated in all, and no major adverse events (AEs) were reported. CBD showed efficacy in patients with drug‐resistant epilepsy due to SYNGAP1 mutations. Other patients with rare genetic developmental and epileptic encephalopathies with drug‐resistant epilepsies might benefit from CBD.