bluuebunny/crossref_metadata_2025 huggingface dataset:
Ibuprofen and indomethacin differentially regulate vascular endothelial growth factor and its receptors in ductus arteriosus endothelial cells
Authors: Sallmon Hannes , Akanbi Sandra , Weber Sven C. , Gratopp Alexander , Rheinländer Cornelia , Koehne Petra
Published: December 2017

Background

Cyclooxygenase inhibitors are widely applied to facilitate ductal closure in preterm infants. The mechanisms that lead to patent ductus arteriosus closure are incompletely understood. Vascular endothelial growth factor plays pivotal roles during ductal closure and remodelling.

Aim

The aim of this study was to investigate the effects of ibuprofen and indomethacin on the expression of vascular endothelial growth factor and its receptors in a primary rat ductus arteriosus endothelial cell culture.

Methods

Protein expression of vascular endothelial growth factor and vascular endothelial growth factor receptor 1 and 2 was confirmed in rat ductus arteriosus and aorta by immunofluorescence staining. Fetal rat endothelial cells were isolated from ductus arteriosus and aorta using immunomagnetic cell sorting and treated with ibuprofen or indomethacin. mRNA expression levels were assessed by quantitative polymerase chain reaction analysis.

Results

In ductal endothelial cells, ibuprofen significantly induced vascular endothelial growth factor and its receptor 2, but not receptor 1, whereas indomethacin did not alter the expression levels of the vascular endothelial growth factor system. In contrast, ibuprofen significantly induced vascular endothelial growth factor and its receptors 1 and 2 in aortic endothelial cells, whereas indomethacin only induced vascular endothelial growth factor receptor 2.

Conclusion

Our results indicate differential effects of ibuprofen and indomethacin on the expression levels of the vascular endothelial growth factor system in ductus arteriosus endothelial cells. In addition, vessel-specific differences between ductal and aortic endothelial cells were found. Further in vivo studies are needed to elucidate the biological significance of these findings.
Neuropsychological Investigations of Human Amnesia: Insights Into the Role of the Medial Temporal Lobes in Cognition
Authors: Verfaellie Mieke , Keane Margaret M.
Published: December 2017

The past 30 years of research on human amnesia has yielded important changes in our understanding of the role of the medial temporal lobes (MTL) in memory. On the one hand, this body of evidence has highlighted that not all types of memory are impaired in patients with MTL lesions. On the other hand, this research has made apparent that the role of the MTL extends beyond the domain of long-term memory, to include working memory, perception, and future thinking. In this article, we review the discoveries and controversies that have characterized this literature and that set the stage for a new conceptualization of the role of the MTL in cognition. This shift toward a more nuanced understanding of MTL function has direct relevance for a range of clinical disorders in which the MTL is implicated, potentially shaping not only theoretical understanding but also clinical practice. (JINS, 2017, 23, 732–740)
Does Cannabis Use Cause Declines in Neuropsychological Functioning? A Review of Longitudinal Studies
Authors: Gonzalez Raul , Pacheco-Colón Ileana , Duperrouzel Jacqueline C. , Hawes Samuel W.
Published: December 2017

Cannabis use has been linked to impairments in neuropsychological functioning across a large and continually expanding body of research. Yet insight into underlying causal relations remains limited due to the historically cross-sectional nature of studies in this area. Recently, however, studies have begun to use more informative design strategies to delineate these associations. The aim of this article is to provide a critical evaluation and review of research that uses longitudinal designs to examine the link between cannabis use and neuropsychological functioning. In summarizing the primary findings across these studies, this review suggests that cannabis use leads to neuropsychological decline. However, across most studies, these associations were modest, were present only for the group with the heaviest cannabis use, and were often attenuated (or no longer significant) after controlling for potential confounding variables. Future studies with neuropsychological data before and after initiation of cannabis use, along with careful measurement and control of “shared risk factors” between cannabis use and poorer neuropsychological outcomes, are needed to better understand who, and under what conditions, is most vulnerable to cannabis-associated neuropsychological decline. (JINS, 2017, 23, 893–902)
Attention-Deficit/Hyperactivity Disorder: A Historical Neuropsychological Perspective
Authors: Mahone E. Mark , Denckla Martha B.
Published: December 2017

The behavior patterns of hyperactivity, impulsivity and inattention that would ultimately become recognized as Attention-Deficit Hyperactivity Disorder (ADHD) have been described for centuries. Nevertheless, in the past 35 years, advances in diagnostic methods, identification of biomarkers, and treatments have advanced at an exponential rate. ADHD is now recognized as the most common behavioral disorder of childhood, with risks extending well into adulthood for both males and females, leading to its identification as a significant public health issue. This historical neuropsychological review of ADHD emphasizes scientific highlights in the past 35 years related to ADHD, including the evolution of the diagnosis (from Hyperkinetic Reaction of Childhood to ADHD), influential theories (executive functions, cognitive-energetic, delay aversion), landmark treatment studies (Multimodal Treatment of ADHD [MTA] and Preschool ADHD Treatment Study [PATS]), and advances in brain mapping techniques (anatomic, functional, and resting state magnetic resonance imaging, diffusion tensor imaging). The review concludes by highlighting the challenges of studying and treating a heterogeneous neurodevelopmental disorder like ADHD, with emphasis on associated disorders and conditions (learning disabilities, sluggish cognitive tempo), special populations (girls, preschoolers, adults), and recommendations for scientific inquiry in the next 35 years. Neuropsychologists are well positioned to address the clinical and research challenges of the next generation of studies, especially involving advances in understanding the sexual dimor.phism, full developmental course, and dynamic risks associated with ADHD. (JINS, 2017, 23, 916–929)
Neuropsychology of Multiple Sclerosis: Looking Back and Moving Forward
Authors: Benedict Ralph H.B. , DeLuca John , Enzinger Christian , Geurts Jeroen J.G. , Krupp Lauren B. , Rao Stephen M.
Published: December 2017

The neuropsychological aspects of multiple sclerosis (MS) have evolved over the past three decades. What was once thought to be a rare occurrence, cognitive dysfunction is now viewed as one of the most disabling symptoms of the disease, with devastating effects on patients’ quality of life. This selective review will highlight major innovations and scientific discoveries in the areas of neuropathology, neuroimaging, diagnosis, and treatment that pertain to our understanding of the neuropsychological aspects of MS. Specifically, we focus on the recent discovery that MS produces pathogical lesions of gray matter (GM) that have consequences for cognitive functions. Methods for imaging these GM lesions in MS are discussed along with multimodal imaging studies that integrate structural and functional imaging methods to provide a better understanding of the relationship between cognitive test performance and functional reserve. Innovations in the screening and comprehensive assessment of cognitive disorders are presented along with recent research that examines cognitive dysfunction in pediatric MS. Results of innovative outcome studies in cognitive rehabilitation are discussed. Finally, we highlight trends for potential future innovations over the next decade. (JINS, 2017, 23, 832–842)
Neuropsychology of Learning Disabilities: The Past and the Future
Authors: Fletcher Jack M. , Grigorenko Elena L.
Published: December 2017

Over the past 50 years, research on children and adults with learning disabilities has seen significant advances. Neuropsychological research historically focused on the administration of tests sensitive to brain dysfunction to identify putative neural mechanisms underlying learning disabilities that would serve as the basis for treatment. Led by research on classifying and identifying learning disabilities, four pivotal changes in research paradigms have produced a contemporary scientific, interdisciplinary, and international understanding of these disabilities. These changes are (1) the emergence of cognitive science, (2) the development of quantitative and molecular genetics, (3) the advent of noninvasive structural and functional neuroimaging, and (4) experimental trials of interventions focused on improving academic skills and addressing comorbid conditions. Implications for practice indicate a need to move neuropsychological assessment away from a primary focus on systematic, comprehensive assessment of cognitive skills toward more targeted performance-based assessments of academic achievement, comorbid conditions, and intervention response that lead directly to evidence-based treatment plans. Future research will continue to cross disciplinary boundaries to address questions regarding the interaction of neurobiological and contextual variables, the importance of individual differences in treatment response, and an expanded research base on (a) the most severe cases, (b) older people with LDs, and (c) domains of math problem solving, reading comprehension, and written expression. (JINS, 2017, 23, 930–940)
Medical students’ attitudes towards participating in a palliative medicine course: A new specialty in Israel
Authors: Bar-Sela Gil , Mitnik Inbal , Zalman Daniela , Flechter Ezequiel , Sheinman-Yuffe Hedva , Vulfsons Simon , Postovsky Sergey , Smolin Bella , Nave Rachel , Azzam Zaher S.
Published: December 2017

Background

Palliative medicine is a growing field in Israel, and its training program is still in process. The current study aimed to evaluate students’ attitudes regarding a course in palliative care established in a division of oncology.

Method

Some 45 medical students in their 5th to 6th years participated in a one-week course on palliative care. At the end of each training week, students were asked to complete a questionnaire, evaluating their attitudes regarding different aspects of the program content, such as its importance and relevance to their training as physicians, as well as the contribution of specific parts of the program to their knowledge regarding palliative care.

Results

The overall satisfaction of the 45 students was high. The most contributory parts of the course were the multidisciplinary team and the complementary and alternative medicine. Participating in the staff meetings and accompanying physicians in their daily work were scored as the least contributory parts.

Significance of results

This preliminary study demonstrated students’ overall high satisfaction with the newly established palliative care course and their need for more practical skills. Future studies should investigate and evaluate educational programs in palliative care in order to establish suitable training for medical students.
Overcrowding under the disciplinary umbrella: challenges of investigating and punishing sexual misconduct cases in universities
Authors: Freer Elaine A.O. , Johnson Andrew D.
Published: December 2017

The last year has seen a revolt against the recommendations of the Zellick Report (1994) in England and Wales, and pressure on universities worldwide to bring serious criminal conduct within their own disciplinary structures. This paper examines the reasons why the Zellick Report advised against this, and why higher-education institutions have now turned their back on a number of its recommendations. Factors including student pressure and concerns about low conviction rates for sexual offences in the criminal courts have been cited, but this paper argues that universities will struggle to create a disciplinary system that is fair to both those who are accused of such offences and those who have been victims of them. A recent Universities UK report has reversed the Zellick guidance that conduct amounting to a serious criminal offence should never be pursued under university disciplinary structures. Drawing on both authors’ experiences as practitioners, and using the first author's experience of university disciplinary matters as a case-study, this paper reviews the practical problems of bringing such serious conduct under university disciplinary structures, focusing particularly on the intersection of criminal and internal disciplinary proceedings. It concludes by suggesting possible ways of ameliorating these.
Analysis of Pseudohomophone Orthographic Errors through Functional Magnetic Resonance Imaging (fMRI)
Authors: Guardia-Olmos Joan , Zarabozo-Hurtado Daniel , Peró-Cebollero Maribe , Gudayol-Farré Esteban , Gómez-Velázquez Fabiola R. , González-Garrido Andrés
Published: December 2017

The study of orthographic errors in a transparent language such as Spanish is an important topic in relation to writing acquisition because in Spanish it is common to write pseudohomophones as valid words. The main objective of the present study was to explore the possible differences in activation patterns in brain areas while processing pseudohomophone orthographic errors between participants with high (High Spelling Skills (HSS)) and low (Low Spelling Skills (LSS)) spelling orthographic abilities. We hypothesize that (a) the detection of orthographic errors will activate bilateral inferior frontal gyri, and that (b) this effect will be greater in the HSS group. Two groups of 12 Mexican participants, each matched by age, were formed based on their results in a group of spelling-related ad hoc tests: HSS and LSS groups. During the fMRI session, two experimental tasks were applied involving correct and pseudohomophone substitution of Spanish words. First, a spelling recognition task and second a letter searching task. The LSS group showed, as expected, a lower number of correct responses (F(1, 21) = 52.72, p <.001, η2 = .715) and higher reaction times compared to the HSS group for the spelling task (F(1, 21) = 60.03, p <.001, η2 = .741). However, this pattern was reversed when the participants were asked to decide on the presence of a vowel in the words, regardless of spelling. The fMRI data showed an engagement of the right inferior frontal gyrus in HSS group during the spelling task. However, temporal, frontal, and subcortical brain regions of the LSS group were activated during the same task.
Inter and intra-hemispheric structural imaging markers predict depression relapse after electroconvulsive therapy: a multisite study
Authors: Wade Benjamin S. C. , Sui Jing , Hellemann Gerhard , Leaver Amber M. , Espinoza Randall T. , Woods Roger P. , Abbott Christopher C. , Joshi Shantanu H. , Narr Katherine L.
Published: December 2017

Relapse of depression following treatment is high. Biomarkers predictive of an individual’s relapse risk could provide earlier opportunities for prevention. Since electroconvulsive therapy (ECT) elicits robust and rapidly acting antidepressant effects, but has a >50% relapse rate, ECT presents a valuable model for determining predictors of relapse-risk. Although previous studies have associated ECT-induced changes in brain morphometry with clinical response, longer-term outcomes have not been addressed. Using structural imaging data from 42 ECT-responsive patients obtained prior to and directly following an ECT treatment index series at two independent sites (UCLA: n = 17, age = 45.41±12.34 years; UNM: n = 25; age = 65.00±8.44), here we test relapse prediction within 6-months post-ECT. Random forests were used to predict subsequent relapse using singular and ratios of intra and inter-hemispheric structural imaging measures and clinical variables from pre-, post-, and pre-to-post ECT. Relapse risk was determined as a function of feature variation. Relapse was well-predicted both within site and when cohorts were pooled where top-performing models yielded balanced accuracies of 71–78%. Top predictors included cingulate isthmus asymmetry, pallidal asymmetry, the ratio of the paracentral to precentral cortical thickness and the ratio of lateral occipital to pericalcarine cortical thickness. Pooling cohorts and predicting relapse from post-treatment measures provided the best classification performances. However, classifiers trained on each age-disparate cohort were less informative for prediction in the held-out cohort. Post-treatment structural neuroimaging measures and the ratios of connected regions commonly implicated in depression pathophysiology are informative of relapse risk. Structural imaging measures may have utility for devising more personalized preventative medicine approaches.
Whole-genome sequencing for an enhanced understanding of genetic variation among South Africans
Authors: Choudhury Ananyo , Ramsay Michèle , Hazelhurst Scott , Aron Shaun , Bardien Soraya , Botha Gerrit , Chimusa Emile R. , Christoffels Alan , Gamieldien Junaid , Sefid-Dashti Mahjoubeh J. , Joubert Fourie , Meintjes Ayton , Mulder Nicola , Ramesar Raj , Rees Jasper , Scholtz Kathrine , Sengupta Dhriti , Soodyall Himla , Venter Philip , Warnich Louise , Pepper Michael S.
Published: December 2017

The Southern African Human Genome Programme is a national initiative that aspires to unlock the unique genetic character of southern African populations for a better understanding of human genetic diversity. In this pilot study the Southern African Human Genome Programme characterizes the genomes of 24 individuals (8 Coloured and 16 black southeastern Bantu-speakers) using deep whole-genome sequencing. A total of ~16 million unique variants are identified. Despite the shallow time depth since divergence between the two main southeastern Bantu-speaking groups (Nguni and Sotho-Tswana), principal component analysis and structure analysis reveal significant (p < 10−6) differentiation, and FSTanalysis identifies regions with high divergence. The Coloured individuals show evidence of varying proportions of admixture with Khoesan, Bantu-speakers, Europeans, and populations from the Indian sub-continent. Whole-genome sequencing data reveal extensive genomic diversity, increasing our understanding of the complex and region-specific history of African populations and highlighting its potential impact on biomedical research and genetic susceptibility to disease.
Highly enantioselective catalytic synthesis of chiral pyridines
Authors: Jumde Ravindra P. , Lanza Francesco , Pellegrini Tilde , Harutyunyan Syuzanna R.
Published: December 2017

General methods to prepare chiral pyridine derivatives are greatly sought after due to their significance in medicinal chemistry. Here, we report highly enantioselective catalytic transformations of poorly reactive β-substituted alkenyl pyridines to access a wide range of alkylated chiral pyridines. The simple methodology involves reactivity enhancement via Lewis acid (LA) activation, the use of readily available and highly reactive Grignard reagents, and a copper-chiral diphosphine ligand catalyst. Apart from allowing the introduction of different linear, branched, cyclic, and functionalised alkyl chains at the β-position of alkenyl pyridines, the catalytic system also shows high functional group tolerance.
Bri2 BRICHOS client specificity and chaperone activity are governed by assembly state
Authors: Chen Gefei , Abelein Axel , Nilsson Harriet E. , Leppert Axel , Andrade-Talavera Yuniesky , Tambaro Simone , Hemmingsson Lovisa , Roshan Firoz , Landreh Michael , Biverstål Henrik , Koeck Philip J. B. , Presto Jenny , Hebert Hans , Fisahn André , Johansson Jan
Published: December 2017

Protein misfolding and aggregation is increasingly being recognized as a cause of disease. In Alzheimer’s disease the amyloid-β peptide (Aβ) misfolds into neurotoxic oligomers and assembles into amyloid fibrils. The Bri2 protein associated with Familial British and Danish dementias contains a BRICHOS domain, which reduces Aβ fibrillization as well as neurotoxicity in vitro and in a Drosophila model, but also rescues proteins from irreversible non-fibrillar aggregation. How these different activities are mediated is not known. Here we show that Bri2 BRICHOS monomers potently prevent neuronal network toxicity of Aβ, while dimers strongly suppress Aβ fibril formation. The dimers assemble into high-molecular-weight oligomers with an apparent two-fold symmetry, which are efficient inhibitors of non-fibrillar protein aggregation. These results indicate that Bri2 BRICHOS affects qualitatively different aspects of protein misfolding and toxicity via different quaternary structures, suggesting a means to generate molecular chaperone diversity.
Polymorphic design of DNA origami structures through mechanical control of modular components
Authors: Lee Chanseok , Lee Jae Young , Kim Do-Nyun
Published: December 2017

Scaffolded DNA origami enables the bottom-up fabrication of diverse DNA nanostructures by designing hundreds of staple strands, comprised of complementary sequences to the specific binding locations of a scaffold strand. Despite its exceptionally high design flexibility, poor reusability of staples has been one of the major hurdles to fabricate assorted DNA constructs in an effective way. Here we provide a rational module-based design approach to create distinct bent shapes with controllable geometries and flexibilities from a single, reference set of staples. By revising the staple connectivity within the desired module, we can control the location, stiffness, and included angle of hinges precisely, enabling the construction of dozens of single- or multiple-hinge structures with the replacement of staple strands up to 12.8% only. Our design approach, combined with computational shape prediction and analysis, can provide a versatile and cost-effective procedure in the design of DNA origami shapes with stiffness-tunable units.
Fluctuations in instantaneous frequency predict alpha amplitude during visual perception
Authors: Nelli Stephanie , Itthipuripat Sirawaj , Srinivasan Ramesh , Serences John T.
Published: December 2017

Rhythmic neural activity in the alpha band (8–13 Hz) is thought to have an important role in the selective processing of visual information. Typically, modulations in alpha amplitude and instantaneous frequency are thought to reflect independent mechanisms impacting dissociable aspects of visual information processing. However, in complex systems with interacting oscillators such as the brain, amplitude and frequency are mathematically dependent. Here, we record electroencephalography in human subjects and show that both alpha amplitude and instantaneous frequency predict behavioral performance in the same visual discrimination task. Consistent with a model of coupled oscillators, we show that fluctuations in instantaneous frequency predict alpha amplitude on a single trial basis, empirically demonstrating that these metrics are not independent. This interdependence suggests that changes in amplitude and instantaneous frequency reflect a common change in the excitatory and inhibitory neural activity that regulates alpha oscillations and visual information processing.
Patterns of biophonic periodicity on coral reefs in the Great Barrier Reef
Authors: McWilliam Jamie N. , McCauley Robert D. , Erbe Christine , Parsons Miles J. G.
Published: December 2017

The coral reefs surrounding Lizard Island in the Great Barrier Reef have a diverse soundscape that contains an array of bioacoustic phenomena, notably choruses produced by fishes. Six fish choruses identified around Lizard Island exhibited distinctive spatial and temporal patterns from 2014 to 2016. Several choruses displayed site fidelity, indicating that particular sites may represent important habitat for fish species, such as fish spawning aggregations sites. The choruses displayed a broad range of periodicities, from diel to annual, which provides new insights into the ecology of vocalising reef fish species and the surrounding ecosystem. All choruses were affected by one or more environmental variables including temperature and moonlight, the latter of which had a significant influence on the timing and received sound levels. These findings highlight the utility of passive acoustic tools for long-term monitoring and management of coral reefs, which is highly relevant in light of recent global disturbance events, particularly coral bleaching.
N-acetylcysteine-functionalized coating avoids bacterial adhesion and biofilm formation
Authors: Costa Fabíola , Sousa Daniela M. , Parreira Paula , Lamghari Meriem , Gomes Paula , Martins M. Cristina L.
Published: December 2017

N-acetyl cysteine (NAC) is an FDA-approved drug clinically applied on a broad range of pathologies. Further research has been conducted with this drug to benefit from its antimicrobial activity potential. However, NAC has a very short half-life and therefore strategies that accomplish high local concentrations would be beneficial. In this study, covalent immobilization of NAC was performed, in order to obtain long-lasting high local concentration of the drug onto a chitosan(Ch)-derived implant-related coating. For the development of NAC-functionalized Ch films, water-based carbodiimide chemistry was applied to avoid the use of toxic organic solvents. Here we report the optimization steps performed to immobilize NAC onto the surface of pre-prepared Ch coatings, to ensure full exposure of NAC. Surface characterization using ellipsometry, water contact angle measurements and X-ray photoelectron spectroscopy (XPS), demonstrated the success of NAC immobilization at 4 mg/mL. Quartz crystal microbalance with dissipation (QCM-D) demonstrated that surface immobilized NAC decreases protein adsorption to Ch coatings. Biological studies confirmed that immobilized NAC4 avoids methicillin-resistant Staphylococcus aureus adhesion to Ch coating, impairing biofilm formation, without inducing cytotoxic effects. This is particularly interesting towards further developments as a prevention coating.
Lagrangian Statistics and Intermittency in Gulf of Mexico
Authors: Lin Liru , Zhuang Wei , Huang Yongxiang
Published: December 2017

Due to the nonlinear interaction between different flow patterns, for instance, ocean current, meso-scale eddies, waves, etc, the movement of ocean is extremely complex, where a multiscale statistics is then relevant. In this work, a high time-resolution velocity with a time step 15 minutes obtained by the Lagrangian drifter deployed in the Gulf of Mexico (GoM) from July 2012 to October 2012 is considered. The measured Lagrangian velocity correlation function shows a strong daily cycle due to the diurnal tidal cycle. The estimated Fourier power spectrum E(f) implies a dual-power-law behavior which is separated by the daily cycle. The corresponding scaling exponents are close to −1.75 and −2.75 respectively for the time scale larger (resp. 0.1 ≤ f ≤ 0.4 day−1) and smaller (resp. 2 ≤ f ≤ 8 day−1) than 1 day. A Hilbert-based approach is then applied to this data set to identify the possible multifractal property of the cascade process. The results show an intermittent dynamics for the time scale larger than 1 day, while a less intermittent dynamics for the time scale smaller than 1 day. It is speculated that the energy is partially injected via the diurnal tidal movement and then transferred to larger and small scales through a complex cascade process, which needs more studies in the near future.
Effect of carnosine supplementation on the plasma lipidome in overweight and obese adults: a pilot randomised controlled trial
Authors: Baye Estifanos , Ukropec Jozef , de Courten Maximilian PJ , Vallova Silvia , Krumpolec Patrik , Kurdiova Timea , Aldini Giancarlo , Ukropcova Barbara , de Courten Barbora
Published: December 2017

Carnosine has been shown to reduce oxidation and glycation of low density lipoprotein hence improving dyslipidaemia in rodents. The effect of carnosine on human plasma lipidome has thus far not been investigated. We aimed to determine whether carnosine supplementation improves the plasma lipidome in overweight and obese individuals. Lipid analysis was performed by liquid chromatography mass spectrometry in 24 overweight and obese adults: 13 were randomly assigned to 2 g carnosine daily and 11 to placebo, and treated for 12 weeks. Carnosine supplementation maintained trihexosylceramide (0.01 ± 0.19 vs −0.28 ± 0.34 nmol/ml, p = 0.04), phosphatidylcholine (77 ± 167 vs −81 ± 196 nmol/ml, p = 0.01) and free cholesterol (20 ± 80 vs −69 ± 80 nmol/ml, p = 0.006) levels compared to placebo. Trihexosylceramide was inversely related with fasting insulin (r = −0.6, p = 0.002), insulin resistance (r = −0.6, p = 0.003), insulin secretion (r = −0.4, p = 0.05) and serum carnosinase 1 activity (r = −0.3, p = 0.05). Both phosphatidylcholine and free cholesterol did not correlate with any cardiometabolic parameters. Our data suggest that carnosine may have beneficial effects on the plasma lipidome. Future larger clinical trials are needed to confirm this.
Multipulse sodium magnetic resonance imaging for multicompartment quantification: Proof-of-concept
Authors: Gilles Alina , Nagel Armin M. , Madelin Guillaume
Published: December 2017

We present a feasibility study of sodium quantification in a multicompartment model of the brain using sodium (23Na) magnetic resonance imaging. The proposed method is based on a multipulse sequence acquisition and simulation at 7 T, which allows to differentiate the 23Na signals emanating from three compartments in human brain in vivo: intracellular (compartment 1), extracellular (compartment 2), and cerebrospinal fluid (compartment 3). The intracellular sodium concentration C1 and the volume fractions α1, α2, and α3 of all respective three brain compartments can be estimated. Simulations of the sodium spin 3/2 dynamics during a 15-pulse sequence were used to optimize the acquisition sequence by minimizing the correlation between the signal evolutions from the three compartments. The method was first tested on a three-compartment phantom as proof-of-concept. Average values of the 23Na quantifications in four healthy volunteer brains were α1 = 0.54 ± 0.01, α2 = 0.23 ± 0.01, α3 = 1.03 ± 0.01, and C1 = 23 ± 3 mM, which are comparable to the expected physiological values $${{\boldsymbol{\alpha }}}_{{\bf{1}}}^{{\boldsymbol{theory}}}$$

α

1

theory

∼ 0.6, $${{\boldsymbol{\alpha }}}_{{\bf{2}}}^{{\boldsymbol{theory}}}$$

α

2

theory

∼ 0.2, $${{\boldsymbol{\alpha }}}_{{\bf{3}}}^{{\boldsymbol{theory}}}$$

α

3

theory

∼ 1, and $${{\boldsymbol{C}}}_{{\bf{1}}}^{{\boldsymbol{theory}}}$$

C

1

theory

∼ 10–30 mM. The proposed method may allow a quantitative assessment of the metabolic role of sodium ions in cellular processes and their malfunctions in brain in vivo.
Development of Erasin: a chromone-based STAT3 inhibitor which induces apoptosis in Erlotinib-resistant lung cancer cells
Authors: Lis Christian , Rubner Stefan , Roatsch Martin , Berg Angela , Gilcrest Tyler , Fu Darwin , Nguyen Elizabeth , Schmidt Anne-Marie , Krautscheid Harald , Meiler Jens , Berg Thorsten
Published: December 2017

Inhibition of protein-protein interactions by small molecules offers tremendous opportunities for basic research and drug development. One of the fundamental challenges of this research field is the broad lack of available lead structures from nature. Here, we demonstrate that modifications of a chromone-based inhibitor of the Src homology 2 (SH2) domain of the transcription factor STAT5 confer inhibitory activity against STAT3. The binding mode of the most potent STAT3 inhibitor Erasin was analyzed by the investigation of structure-activity relationships, which was facilitated by chemical synthesis and biochemical activity analysis, in combination with molecular docking studies. Erasin inhibits tyrosine phosphorylation of STAT3 with selectivity over STAT5 and STAT1 in cell-based assays, and increases the apoptotic rate of cultured NSCLC cells in a STAT3-dependent manner. This ability of Erasin also extends to HCC-827 cells with acquired resistance against Erlotinib, a clinically used inhibitor of the EGF receptor. Our work validates chromone-based acylhydrazones as privileged structures for antagonizing STAT SH2 domains, and demonstrates that apoptosis can be induced in NSCLC cells with acquired Erlotinib resistance by direct inhibition of STAT3.
Bulky Lesion Bypass Requires Dpo4 Binding in Distinct Conformations
Authors: Liyanage Pramodha S. , Walker Alice R. , Brenlla Alfonso , Cisneros G. Andrés , Romano Louis J. , Rueda David
Published: December 2017

Translesion DNA synthesis is an essential process that helps resume DNA replication at forks stalled near bulky adducts on the DNA. Benzo[a]pyrene (B[a]P) is a polycyclic aromatic hydrocarbon (PAH) that can be metabolically activated to benzo[a]pyrene diol epoxide (BPDE), which then can react with DNA to form carcinogenic DNA adducts. Here, we have used single-molecule florescence resonance energy transfer (smFRET) experiments, classical molecular dynamics simulations, and nucleotide incorporation assays to investigate the mechanism by which the model Y-family polymerase, Dpo4, bypasses a (+)-cis-B[a]P-N2-dG adduct in DNA. Our data show that when (+)-cis-B[a]P-N2-dG is the templating base, the B[a]P moiety is in a non-solvent exposed conformation stacked within the DNA helix, where it effectively blocks nucleotide incorporation across the adduct by Dpo4. However, when the media contains a small amount of dimethyl sulfoxide (DMSO), the adduct is able to move to a solvent-exposed conformation, which enables error-prone DNA replication past the adduct. When the primer terminates across from the adduct position, the addition of DMSO leads to the formation of an insertion complex capable of accurate nucleotide incorporation.
A Wide Dynamic Range Polarization Sensing Long Wave Infrared Detector
Authors: Mohammadi Elham , Behdad Nader
Published: December 2017

We present the design, fabrication, and characterization of an infrared (IR) polarization sensing detector with a wide dynamic range and sub-wavelength dimensions. The detector consists of two orthogonal slot antennas, each loaded with two microbolometers at its edges. The polarization of the incoming IR radiation is detected by comparing the received power levels in the bolometer pairs corresponding to each slot antenna. The IR radiation is sensed by applying a dc bias voltage to each antenna and measuring the changes in the dc current caused by the change of the bolometer resistance as they absorb the incoming IR radiation. In this design, the ratio of the absorbed power in the bolometers is a one to one function of the polarization of the incident wave. A prototype of this detector, designed to have maximum sensitivity at λ = 10.6 μm, was designed, fabricated, and characterized. The fabricated detector has an area of 0.7λ × 0.7λ, where λ is the free-space wavelength. The polarization sensing response is characterized under different angles of incidence. The measurement results show that the device has a dynamic range of 24 dB between two orthogonal orientations of EM wave polarization for incidence angles in the range of ±20° from boresight.
Conformational Switch Regulates the DNA Cytosine Deaminase Activity of Human APOBEC3B
Authors: Shi Ke , Demir Özlem , Carpenter Michael A. , Wagner Jeff , Kurahashi Kayo , Harris Reuben S. , Amaro Rommie E. , Aihara Hideki
Published: December 2017

The APOBEC3B (A3B) single-stranded DNA (ssDNA) cytosine deaminase has important roles in innate immunity but is also a major endogenous source of mutations in cancer. Previous structural studies showed that the C-terminal catalytic domain of human A3B has a tightly closed active site, and rearrangement of the surrounding loops is required for binding to substrate ssDNA. Here we report structures of the A3B catalytic domain in a new crystal form that show alternative, yet still closed, conformations of active site loops. All-atom molecular dynamics simulations support the dynamic behavior of active site loops and recapitulate the distinct modes of interactions that maintain a closed active site. Replacing segments of A3B loop 1 to mimic the more potent cytoplasmic deaminase APOBEC3A leads to elevated ssDNA deaminase activity, likely by facilitating opening of the active site. These data collectively suggest that conformational equilibrium of the A3B active site loops, skewed toward being closed, controls enzymatic activity by regulating binding to ssDNA substrates.
μMAPPS: a novel phasor approach to second harmonic analysis for in vitro-in vivo investigation of collagen microstructure
Authors: Radaelli F. , D’Alfonso L. , Collini M. , Mingozzi F. , Marongiu L. , Granucci F. , Zanoni I. , Chirico G. , Sironi L.
Published: December 2017

Second Harmonic Generation (SHG) is a label-free imaging method used to monitor collagen organization in tissues. Due to its sensitivity to the incident polarization, it provides microstructural information otherwise unreachable by other intensity based imaging methods. We develop and test a Microscopic Multiparametric Analysis by Phasor projection of Polarization-dependent SHG (μMAPPS) that maps the features of the collagen architecture in tissues at the micrometer scale. μMAPPS retrieves pixel-by-pixel the collagen fibrils anisotropy and orientation by operating directly on two coupled phasor spaces, avoiding direct fitting of the polarization dependent SHG signal. We apply μMAPPS to fixed tissue sections and to the study of the collagen microscopic organization in tumors ex-vivo and in-vivo. We develop a clustering algorithm to automatically group pixels with similar microstructural features. μMAPPS can perform fast analyses of tissues and opens to future applications for in-situ diagnosis of pathologies and diseases that could assist histo-pathological evaluation.
Comparative epidemiology of poliovirus transmission
Authors: Noori Navideh , Drake John M. , Rohani Pejman
Published: December 2017

Understanding the determinants of polio transmission and its large-scale epidemiology remains a public health priority. Despite a 99% reduction in annual wild poliovirus (WPV) cases since 1988, tackling the last 1% has proven difficult. We identified key covariates of geographical variation in polio transmission patterns by relating country-specific annual disease incidence to demographic, socio-economic and environmental factors. We assessed the relative contributions of these variables to the performance of computer-generated models for predicting polio transmission. We also examined the effect of spatial coupling on the polio extinction frequency in islands relative to larger land masses. Access to sanitation, population density, forest cover and routine vaccination coverage were the strongest predictors of polio incidence, however their relative effect sizes were inconsistent geographically. The effect of climate variables on polio incidence was negligible, indicating that a climate effect is not identifiable at the annual scale, suggesting a role for climate in shaping the transmission seasonality rather than intensity. We found polio fadeout frequency to depend on both population size and demography, which should therefore be considered in policies aimed at extinction. Our comparative epidemiological approach highlights the heterogeneity among polio transmission determinants. Recognition of this variation is important for the maintenance of population immunity in a post-polio era.
A molecular chaperone activity of CCS restores the maturation of SOD1 fALS mutants
Authors: Luchinat Enrico , Barbieri Letizia , Banci Lucia
Published: December 2017

Superoxide dismutase 1 (SOD1) is an important metalloprotein for cellular oxidative stress defence, that is mutated in familiar variants of Amyotrophic Lateral Sclerosis (fALS). Some mutations destabilize the apo protein, leading to the formation of misfolded, toxic species. The Copper Chaperone for SOD1 (CCS) transiently interacts with SOD1 and promotes its correct maturation by transferring copper and catalyzing disulfide bond formation. By in vitro and in-cell NMR, we investigated the role of the SOD-like domain of CCS (CCS-D2). We showed that CCS-D2 forms a stable complex with zinc-bound SOD1 in human cells, that has a twofold stabilizing effect: it both prevents the accumulation of unstructured mutant SOD1 and promotes zinc binding. We further showed that CCS-D2 interacts with apo-SOD1 in vitro, suggesting that in cells CCS stabilizes mutant apo-SOD1 prior to zinc binding. Such molecular chaperone function of CCS-D2 is novel and its implications in SOD-linked fALS deserve further investigation.
Enhanced microchip electrophoresis separations combined with electrochemical detection utilizing a capillary embedded in polystyrene
Authors: Mehl Benjamin T. , Martin R. Scott
Published: December 2017

A polystyrene–PDMS device utilizing an embedded fused silica capillary and electrochemical detection was used for improved efficiency separations of catecholamines.
Upconverting nanocomposites with combined photothermal and photodynamic effects
Authors: Huang Yue , Skripka Artiom , Labrador-Páez Lucía , Sanz-Rodríguez Francisco , Haro-González Patricia , Jaque Daniel , Rosei Federico , Vetrone Fiorenzo
Published: December 2017

Upconverting hybrid nanocomposites consisting of gold nanorod cores and decorated with upconverting nanoparticles were prepared for photothermal and photodynamic applications.
Safe core-satellite magneto-plasmonic nanostructures for efficient targeting and photothermal treatment of tumor cells
Authors: Bertorelle F. , Pinto M. , Zappon R. , Pilot R. , Litti L. , Fiameni S. , Conti G. , Gobbo M. , Toffoli G. , Colombatti M. , Fracasso G. , Meneghetti M.
Published: December 2017

Magneto-plasmonic nanostructures functionalized with cell targeting units are of great interest for nanobiotechnology applications.
Designing multifunctional SO3H-based polyoxometalate catalysts for oxidative desulfurization in acid deep eutectic solvents
Authors: Jiang Wei , Dong Lei , Liu Wei , Guo Tao , Li Hongping , Zhang Ming , Zhu Wenshuai , Li Huaming
Published: December 2017

Deep eutectic solvents (DESs) are ‘green’ sustainable solvents with wide applications such as extractive desulfurization of fuel; however, their low extraction efficiency is a major limitation to such applications.
Copper-catalyzed direct coupling of benzoxazin-2-ones with indoles for the synthesis of diverse 3-indolylbenzoxazin-2-ones: access to natural cephalandole A
Authors: Pandit Rameshwar Prasad , Shim Jae-Jin , Kim Sung Hong , Lee Yong Rok
Published: December 2017

Diverse and functionalized 3-indolyl benzo[b][1,4]oxazin-2-ones were synthesized via copper-catalyzed direct coupling of benzo[b][1,4]oxazin-2-one and indoles in air.
Aromatic poly(ether ether ketone)s capable of crosslinking via UV irradiation to improve gas separation performance
Authors: Puertas-Bartolomé María , Dose Michelle E. , Bosch Paula , Freeman Benny D. , McGrath James E. , Riffle Judy S. , Lozano Angel E. , de la Campa José G. , Álvarez Cristina
Published: December 2017

The high reactivity of methyl groups to form radicals in biphenyl-based poly(ether-ether-ketone)s improves the separation performance of the crosslinked membranes.
Glutaredoxins employ parallel monothiol–dithiol mechanisms to catalyze thiol–disulfide exchanges with protein disulfides
Authors: Ukuwela Ashwinie A. , Bush Ashley I. , Wedd Anthony G. , Xiao Zhiguang
Published: December 2017

Glutaredoxins were demonstrated to be a family of versatile enzymes capable of catalyzing thiol–disulfide exchange involving GSSG/GSHviadifferent catalytic routes either alone or in parallel.
Charge carrier trapping processes in lanthanide doped LaPO4, GdPO4, YPO4, and LuPO4
Authors: Lyu Tianshuai , Dorenbos Pieter
Published: December 2017

Various methods for deliberate design of electron and hole trapping materials were explored with a study on double lanthanide doped rare earth ortho phosphates.
Did a stellar fly-by shape the planetary system around Pr 0211 in the cluster M44?
Authors: Pfalzner Susanne , Bhandare Asmita , Vincke Kirsten
Published: December 2017

Aims. Out of the ~3000 exoplanets detected so far, only 14 planets are members of open clusters: one of them is the exoplanet system around Pr 0211 in the cluster M44. The system consists of at least 2 planets, and the outer planet moves on a highly eccentric orbit at 5.5 AU. One hypothesis is that a close fly-by of a neighbouring star was responsible for the eccentric orbit. We test this hypothesis.

Methods. First we determined the type of fly-by that would lead to the observed parameters, and then we used this result to determine the history of such fly-bys in simulations of the early dynamics in an M44-like environment.

Results. We find that although very close fly-bys are required to obtain the observed properties of Pr 0211c, such fly-bys are relatively common as a result of the high stellar density and longevity of the cluster. Such close fly-bys are most frequent during the first 1−2 Myr after cluster formation, corresponding to a cluster age ≤3 Myr. During the first 2 to 3 Myr, about 6.5% of stars experience a fly-by that would lead to such a small system-size as observed for Pr 0211 or even smaller. It is unclear whether planets generally form on such short timescales. However, after this time, the close fly-by rate is still 0.2−0.5 Myr−1, which means that 12−20% of stars would experience such close fly-bys over this time span when we extrapolate the situation to the age of M44.

Conclusions. Our simulations show that the fly-by scenario is a realistic option for the formation of eccentricity orbits of the planets in M44 (Wang et al. 2015). The occurrence of such events is relatively high, leading to the expectation that similar systems are likely common in open clusters in general.
Spitzer secondary eclipses of Qatar-1b
Authors: Garhart Emily , Deming Drake , Mandell Avi , Knutson Heather , Fortney Jonathan J.
Published: December 2017

Aims. Previous secondary eclipse observations of the hot Jupiter Qatar-1b in the Ks band suggest that it may have an unusually high day side temperature, indicative of minimal heat redistribution. There have also been indications that the orbit may be slightly eccentric, possibly forced by another planet in the system. We investigate the day side temperature and orbital eccentricity using secondary eclipse observations with Spitzer.

Methods. We observed the secondary eclipse with Spitzer/IRAC in subarray mode, in both 3.6 and 4.5 μm wavelengths. We used pixel-level decorrelation to correct for Spitzer’s intra-pixel sensitivity variations and thereby obtain accurate eclipse depths and central phases.

Results. Our 3.6 μm eclipse depth is 0.149 ± 0.051% and the 4.5 μm depth is 0.273 ± 0.049%. Fitting a blackbody planet to our data and two recent Ks band eclipse depths indicates a brightness temperature of 1506 ± 71 K. Comparison to model atmospheres for the planet indicates that its degree of longitudinal heat redistribution is intermediate between fully uniform and day-side only. The day side temperature of the planet is unlikely to be as high (1885 K) as indicated by the ground-based eclipses in the Ks band, unless the planet’s emergent spectrum deviates strongly from model atmosphere predictions. The average central phase for our Spitzer eclipses is 0.4984 ± 0.0017, yielding e cos ω = −0.0028 ± 0.0027. Our results are consistent with a circular orbit, and we constrain e cos ω much more strongly than has been possible with previous observations.