bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractThe 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

AbstractGeneral 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

AbstractProtein 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

AbstractScaffolded 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

AbstractRhythmic 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

AbstractThe 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

AbstractN-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

AbstractDue 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

AbstractCarnosine 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

AbstractWe 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

AbstractInhibition 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

AbstractTranslesion 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

AbstractWe 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

AbstractThe 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

AbstractSecond 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

AbstractUnderstanding 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

AbstractSuperoxide 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.