bluuebunny/crossref_metadata_2025 huggingface dataset:
Orientation-dependent Dxz4 contacts shape the 3D structure of the inactive X chromosome
Authors: Bonora G. , Deng X. , Fang H. , Ramani V. , Qiu R. , Berletch J. B. , Filippova G. N. , Duan Z. , Shendure J. , Noble W. S. , Disteche C. M.
Published: April 2018

The mammalian inactive X chromosome (Xi) condenses into a bipartite structure with two superdomains of frequent long-range contacts, separated by a hinge region. Using Hi-C in edited mouse cells with allelic deletions or inversions within the hinge, here we show that the conserved Dxz4 locus is necessary to maintain this bipartite structure. Dxz4 orientation controls the distribution of contacts on the Xi, as shown by a massive reversal in long-range contacts after Dxz4 inversion. Despite an increase in CTCF binding and chromatin accessibility on the Xi in Dxz4-edited cells, only minor changes in TAD structure and gene expression were detected, in accordance with multiple epigenetic mechanisms ensuring X silencing. We propose that Dxz4 represents a structural platform for frequent long-range contacts with multiple loci in a direction dictated by the orientation of its bank of CTCF motifs, which may work as a ratchet to form the distinctive bipartite structure of the condensed Xi.
Publisher Correction: Reversible chromism of spiropyran in the cavity of a flexible coordination cage
Authors: Samanta Dipak , Galaktionova Daria , Gemen Julius , Shimon Linda J. W. , Diskin-Posner Yael , Avram Liat , Král Petr , Klajn Rafal
Published: April 2018

The original version of this Article contained an error in Fig. 4c, in which the right-most chemical structure included an ‘N+’ rather than an ‘N’. This has been corrected in both the PDF and HTML versions of the Article.
Characterising the phenotypic evolution of circulating tumour cells during treatment
Authors: Tsao Simon Chang-Hao , Wang Jing , Wang Yuling , Behren Andreas , Cebon Jonathan , Trau Matt
Published: April 2018

Real-time monitoring of cancer cells’ phenotypic evolution during therapy can provide vital tumour biology information for treatment management. Circulating tumour cell (CTC) analysis has emerged as a useful monitoring tool, but its routine usage is restricted by either limited multiplexing capability or sensitivity. Here, we demonstrate the use of antibody-conjugated and Raman reporter-coated gold nanoparticles for simultaneous labelling and monitoring of multiple CTC surface markers (named as “cell signature”), without the need for isolating individual CTCs. We observe cell heterogeneity and phenotypic changes of melanoma cell lines during molecular targeted treatment. Furthermore, we follow the CTC signature changes of 10 stage-IV melanoma patients receiving immunological or molecular targeted therapies. Our technique maps the phenotypic evolution of patient CTCs sensitively and rapidly, and shows drug-resistant clones having different CTC signatures of potential clinical value. We believe our proposed method is of general interest in the CTC relevant research and translation fields.
Chirality-controlled crystallization via screw dislocations
Authors: Sung Baeckkyoung , de la Cotte Alexis , Grelet Eric
Published: April 2018

Chirality plays an important role in science from enantiomeric separation in chemistry to chiral plasmonics in nanotechnology. However, the understanding of chirality amplification from chiral building blocks to ordered helical superstructures remains a challenge. Here, we demonstrate that topological defects, such as screw dislocations, can drive the chirality transfer from particle to supramolecular structure level during the crystallization process. By using a model system of chiral particles, which enables direct imaging of single particle incorporation into growing crystals, we show that the crystallization kinetic pathway is the key parameter for monitoring, via the defects, the chirality amplification of the crystalline structures from racemic to predominantly homohelical. We provide an explanation based on the interplay between geometrical frustration, racemization induced by thermal fluctuations, and particle chirality. Our results demonstrate that screw dislocations not only promote the growth, but also control the chiral morphology and therefore the functionality of crystalline states.
Rapid increase in atmospheric iodine levels in the North Atlantic since the mid-20th century
Authors: Cuevas Carlos A. , Maffezzoli Niccolò , Corella Juan Pablo , Spolaor Andrea , Vallelonga Paul , Kjær Helle A. , Simonsen Marius , Winstrup Mai , Vinther Bo , Horvat Christopher , Fernandez Rafael P. , Kinnison Douglas , Lamarque Jean-François , Barbante Carlo , Saiz-Lopez Alfonso
Published: April 2018

Atmospheric iodine causes tropospheric ozone depletion and aerosol formation, both of which have significant climate impacts, and is an essential dietary element for humans. However, the evolution of atmospheric iodine levels at decadal and centennial scales is unknown. Here, we report iodine concentrations in the RECAP ice-core (coastal East Greenland) to investigate how atmospheric iodine levels in the North Atlantic have evolved over the past 260 years (1750–2011), this being the longest record of atmospheric iodine in the Northern Hemisphere. The levels of iodine tripled from 1950 to 2010. Our results suggest that this increase is driven by anthropogenic ozone pollution and enhanced sub-ice phytoplankton production associated with the recent thinning of Arctic sea ice. Increasing atmospheric iodine has accelerated ozone loss and has considerably enhanced iodine transport and deposition to the Northern Hemisphere continents. Future climate and anthropogenic forcing may continue to amplify oceanic iodine emissions with potentially significant health and environmental impacts at global scale.
AKAPs-PKA disruptors increase AQP2 activity independently of vasopressin in a model of nephrogenic diabetes insipidus
Authors: Ando Fumiaki , Mori Shuichi , Yui Naofumi , Morimoto Tetsuji , Nomura Naohiro , Sohara Eisei , Rai Tatemitsu , Sasaki Sei , Kondo Yoshiaki , Kagechika Hiroyuki , Uchida Shinichi
Published: April 2018

Congenital nephrogenic diabetes insipidus (NDI) is characterized by the inability of the kidney to concentrate urine. Congenital NDI is mainly caused by loss-of-function mutations in the vasopressin type 2 receptor (V2R), leading to impaired aquaporin-2 (AQP2) water channel activity. So far, treatment options of congenital NDI either by rescuing mutant V2R with chemical chaperones or by elevating cyclic adenosine monophosphate (cAMP) levels have failed to yield effective therapies. Here we show that inhibition of A-kinase anchoring proteins (AKAPs) binding to PKA increases PKA activity and activates AQP2 channels in cortical collecting duct cells. In vivo, the low molecular weight compound 3,3′-diamino-4,4′-dihydroxydiphenylmethane (FMP-API-1) and its derivatives increase AQP2 activity to the same extent as vasopressin, and increase urine osmolality in the context of V2R inhibition. We therefore suggest that FMP-API-1 may constitute a promising lead compound for the treatment of congenital NDI caused by V2R mutations.
Host-mediated selection impacts the diversity of Plasmodium falciparum antigens within infections
Authors: Early Angela M. , Lievens Marc , MacInnis Bronwyn L. , Ockenhouse Christian F. , Volkman Sarah K. , Adjei Samuel , Agbenyega Tsiri , Ansong Daniel , Gondi Stacey , Greenwood Brian , Hamel Mary , Odero Chris , Otieno Kephas , Otieno Walter , Owusu-Agyei Seth , Asante Kwaku Poku , Sorgho Hermann , Tina Lucas , Tinto Halidou , Valea Innocent , Wirth Dyann F. , Neafsey Daniel E.
Published: April 2018

Host immunity exerts strong selective pressure on pathogens. Population-level genetic analysis can identify signatures of this selection, but these signatures reflect the net selective effect of all hosts and vectors in a population. In contrast, analysis of pathogen diversity within hosts provides information on individual, host-specific selection pressures. Here, we combine these complementary approaches in an analysis of the malaria parasitePlasmodium falciparumusing haplotype sequences from thousands of natural infections in sub-Saharan Africa. We find that parasite genotypes show preferential clustering within multi-strain infections in young children, and identify individual amino acid positions that may contribute to strain-specific immunity. Our results demonstrate that natural host defenses toP. falciparumact in an allele-specific manner to block specific parasite haplotypes from establishing blood-stage infections. This selection partially explains the extreme amino acid diversity of many parasite antigens and suggests that vaccines targeting such proteins should account for allele-specific immunity.
Publisher Correction: Triparental plants provide direct evidence for polyspermy induced polyploidy
Authors: Nakel Thomas , Tekleyohans Dawit G. , Mao Yanbo , Fuchert Golo , Vo Dieu , Groß-Hardt Rita
Published: April 2018

This Article contained errors in Fig. 3 that were brought to our attention by the authors during the production process but, inadvertently, were not corrected before publication. The tick marks on the y-axis in panels b, f, and k, and the median line in the box-and-whisker plot for biparental diploid plants (BP) in panel i were shifted downwards by up to 2 mm. This has now been corrected in both the PDF and HTML versions of the Article
Horn-like space-coiling metamaterials toward simultaneous phase and amplitude modulation
Authors: Ghaffarivardavagh Reza , Nikolajczyk Jacob , Glynn Holt R. , Anderson Stephan , Zhang Xin
Published: April 2018

Acoustic metasurfaces represent a family of planar wavefront-shaping devices garnering increasing attention due to their capacity for novel acoustic wave manipulation. By precisely tailoring the geometry of these engineered surfaces, the effective refractive index may be modulated and, consequently, acoustic phase delays tuned. Despite the successful demonstration of phase engineering using metasurfaces, amplitude modulation remains overlooked. Herein, we present a class of metasurfaces featuring a horn-like space-coiling structure, enabling acoustic control with simultaneous phase and amplitude modulation. The functionality of this class of metasurfaces, featuring a gradient in channel spacing, has been investigated theoretically and numerically and an equivalent model simplifying the structural behavior is presented. A metasurface featuring this geometry has been designed and its functionality in modifying acoustic radiation patterns experimentally validated. This class of acoustic metasurface provides an efficient design methodology enabling complete acoustic wave manipulation, which may find utility in applications including biomedical imaging, acoustic communication, and non-destructive testing.
Unifying the global phylogeny and environmental distribution of ammonia-oxidising archaea based on amoA genes
Authors: Alves Ricardo J. Eloy , Minh Bui Quang , Urich Tim , von Haeseler Arndt , Schleper Christa
Published: April 2018

Ammonia-oxidising archaea (AOA) are ubiquitous and abundant in nature and play a major role in nitrogen cycling. AOA have been studied intensively based on the amoA gene (encoding ammonia monooxygenase subunit A), making it the most sequenced functional marker gene. Here, based on extensive phylogenetic and meta-data analyses of 33,378 curated archaeal amoA sequences, we define a highly resolved taxonomy and uncover global environmental patterns that challenge many earlier generalisations. Particularly, we show: (i) the global frequency of AOA is extremely uneven, with few clades dominating AOA diversity in most ecosystems; (ii) characterised AOA do not represent most predominant clades in nature, including soils and oceans; (iii) the functional role of the most prevalent environmental AOA clade remains unclear; and (iv) AOA harbour molecular signatures that possibly reflect phenotypic traits. Our work synthesises information from a decade of research and provides the first integrative framework to study AOA in a global context.
Reflection from a free carrier front via an intraband indirect photonic transition
Authors: Gaafar Mahmoud A. , Jalas Dirk , O’Faolain Liam , Li Juntao , Krauss Thomas F. , Petrov Alexander Yu. , Eich Manfred
Published: April 2018

The reflection of light from moving boundaries is of interest both fundamentally and for applications in frequency conversion, but typically requires high pump power. By using a dispersion-engineered silicon photonic crystal waveguide, we are able to achieve a propagating free carrier front with only a moderate on-chip peak power of 6 W in a 6 ps-long pump pulse. We employ an intraband indirect photonic transition of a co-propagating probe, whereby the probe practically escapes from the front in the forward direction. This forward reflection has up to 35% efficiency and it is accompanied by a strong frequency upshift, which significantly exceeds that expected from the refractive index change and which is a function of group velocity, waveguide dispersion and pump power. Pump, probe and shifted probe all are around 1.5 µm wavelength which opens new possibilities for “on-chip” frequency manipulation and all-optical switching in optical telecommunications.
Two-dimensional materials in functional three-dimensional architectures with applications in photodetection and imaging
Authors: Lee Wonho , Liu Yuan , Lee Yongjun , Sharma Bhupendra K. , Shinde Sachin M. , Kim Seong Dae , Nan Kewang , Yan Zheng , Han Mengdi , Huang Yonggang , Zhang Yihui , Ahn Jong-Hyun , Rogers John A.
Published: April 2018

Efficient and highly functional three-dimensional systems that are ubiquitous in biology suggest that similar design architectures could be useful in electronic and optoelectronic technologies, extending their levels of functionality beyond those achievable with traditional, planar two-dimensional platforms. Complex three-dimensional structures inspired by origami, kirigami have promise as routes for two-dimensional to three-dimensional transformation, but current examples lack the necessary combination of functional materials, mechanics designs, system-level architectures, and integration capabilities for practical devices with unique operational features. Here, we show that two-dimensional semiconductor/semi-metal materials can play critical roles in this context, through demonstrations of complex, mechanically assembled three-dimensional systems for light-imaging capabilities that can encompass measurements of the direction, intensity and angular divergence properties of incident light. Specifically, the mechanics of graphene and MoS2, together with strategically configured supporting polymer films, can yield arrays of photodetectors in distinct, engineered three-dimensional geometries, including octagonal prisms, octagonal prismoids, and hemispherical domes.
Westward migration of tropical cyclone rapid-intensification over the Northwestern Pacific during short duration El Niño
Authors: Guo Yi-Peng , Tan Zhe-Min
Published: April 2018

The El Niño-Southern Oscillation (ENSO) can significantly affect the rapid intensification of tropical cyclones over the western North Pacific (WNP). However, ENSO events have various durations, which can lead to different atmospheric and oceanic conditions. Here we show that during short duration El Niño events, the WNP tropical cyclone rapid-intensification mean occurrence position migrates westward by ~8.0° longitude, which is caused by reduced vertical wind shear, increased mid-tropospheric humidity, and enhanced tropical cyclone heat potential over the westernmost WNP. The changes in these factors are caused by westward advected upper ocean heat during the decaying phase of a short duration El Niño. As super El Niño events tend to have short durations and their frequency is projected to increase under global warming, our findings have important implications for future projections of WNP tropical cyclone activity.
A switch point in the molecular chaperone Hsp90 responding to client interaction
Authors: Rutz Daniel Andreas , Luo Qi , Freiburger Lee , Madl Tobias , Kaila Ville R. I. , Sattler Michael , Buchner Johannes
Published: April 2018

Heat shock protein 90 (Hsp90) is a dimeric molecular chaperone that undergoes large conformational changes during its functional cycle. It has been established that conformational switch points exist in the N-terminal (Hsp90-N) and C-terminal (Hsp90-C) domains of Hsp90, however information for switch points in the large middle-domain (Hsp90-M) is scarce. Here we report on a tryptophan residue in Hsp90-M as a new type of switch point. Our study shows that this conserved tryptophan senses the interaction of Hsp90 with a stringent client protein and transfers this information via a cation–π interaction with a neighboring lysine. Mutations at this position hamper the communication between domains and the ability of a client protein to affect the Hsp90 cycle. The residue thus allows Hsp90 to transmit information on the binding of a client from Hsp90-M to Hsp90-N which is important for progression of the conformational cycle and the efficient processing of client proteins.
Canonical PI3Kγ signaling in myeloid cells restricts Trypanosoma cruzi infection and dampens chagasic myocarditis
Authors: Silva Maria C. , Davoli-Ferreira Marcela , Medina Tiago S. , Sesti-Costa Renata , Silva Grace K. , Lopes Carla D. , Cardozo Lucas E. , Gava Fábio N. , Lyroni Konstantina , Dias Fabrício C. , Frade Amanda F. , Baron Monique , Nakaya Helder I. , Figueiredo Florêncio , Alves-Filho José C. , Cunha Fernando Q. , Tsatsanis Christos , Chevillard Christophe , Cunha-Neto Edecio , Hirsch Emilio , Silva João S. , Cunha Thiago M.
Published: April 2018

Chagas disease is caused by infection with the protozoan Trypanosoma cruzi (T. cruzi) and is an important cause of severe inflammatory heart disease. However, the mechanisms driving Chagas disease cardiomyopathy have not been completely elucidated. Here, we show that the canonical PI3Kγ pathway is upregulated in both human chagasic hearts and hearts of acutely infected mice. PI3Kγ-deficient mice and mutant mice carrying catalytically inactive PI3Kγ are more susceptible to T. cruzi infection. The canonical PI3Kγ signaling in myeloid cells is essential to restrict T. cruzi heart parasitism and ultimately to avoid myocarditis, heart damage, and death of mice. Furthermore, high PIK3CG expression correlates with low parasitism in human Chagas’ hearts. In conclusion, these results indicate an essential role of the canonical PI3Kγ signaling pathway in the control of T. cruzi infection, providing further insight into the molecular mechanisms involved in the pathophysiology of chagasic heart disease.
The use of electronic alerts in primary care computer systems to identify the excessive prescription of short-acting beta2-agonists for people with asthma: a systematic review
Authors: McKibben Shauna , De Simoni Anna , Bush Andy , Thomas Mike , Griffiths Chris
Published: April 2018

Computers are increasingly used to improve prescribing decisions in the management of long-term conditions however the effects on asthma prescribing remain unclear. We aimed to synthesise the evidence for the use of computerised alerts that identify excessive prescribing of short-acting beta2-agonists (SABAs) to improve asthma management for people with asthma. MEDLINE, CINAHL, Embase, Cochrane and Scopus databases (1990–2016) were searched for randomised controlled trials using electronic alerts to identify excessive prescribing of SABAs for people with asthma in primary care. Inclusion eligibility, quality appraisal (Cochrane risk of bias tool) and data extraction were performed by two independent reviewers. Findings were synthesised narratively. A total of 2035 articles were screened and four trials were eligible. Three studies had low risk of bias: one reported a positive effect on our primary outcome of interest, excessive SABA prescribing; another reported positive effects on the ratio of inhaled corticosteroid (ICS)-SABA prescribing, and asthma control; a third reported no effect on outcomes of interest. One study at high risk of bias reported a reduction in exacerbations and primary care consultations. There is some evidence that electronic alerts reduce excessive prescribing of SABAs, when delivered as part of a multicomponent intervention in an integrated health care system. However due to the variation in health care systems, intervention design and outcomes measured, further research is required to establish optimal design of alerting and intervening systems.
Author Correction: Vertex coloring of graphs via phase dynamics of coupled oscillatory networks
Authors: Parihar Abhinav , Shukla Nikhil , Jerry Matthew , Datta Suman , Raychowdhury Arijit
Published: April 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Diffusion-Limited Growth of Microbial Colonies
Authors: Tronnolone Hayden , Tam Alexander , Szenczi Zoltán , Green J. E. F. , Balasuriya Sanjeeva , Tek Ee Lin , Gardner Jennifer M. , Sundstrom Joanna F. , Jiranek Vladimir , Oliver Stephen G. , Binder Benjamin J.
Published: April 2018

The emergence of diffusion-limited growth (DLG) within a microbial colony on a solid substrate is studied using a combination of mathematical modelling and experiments. Using an agent-based model of the interaction between microbial cells and a diffusing nutrient, it is shown that growth directed towards a nutrient source may be used as an indicator that DLG is influencing the colony morphology. A continuous reaction–diffusion model for microbial growth is employed to identify the parameter regime in which DLG is expected to arise. Comparisons between the model and experimental data are used to argue that the bacterium Bacillus subtilis can undergo DLG, while the yeast Saccharomyces cerevisiae cannot, and thus the non-uniform growth exhibited by this yeast must be caused by the pseudohyphal growth mode rather than limited nutrient availability. Experiments testing directly for DLG features in yeast colonies are used to confirm this hypothesis.
Emotion and anxiety potentiate the way attention alters visual appearance
Authors: Barbot Antoine , Carrasco Marisa
Published: April 2018

The ability to swiftly detect and prioritize the processing of relevant information around us is critical for the way we interact with our environment. Selective attention is a key mechanism that serves this purpose, improving performance in numerous visual tasks. Reflexively attending to sudden information helps detect impeding threat or danger, a possible reason why emotion modulates the way selective attention affects perception. For instance, the sudden appearance of a fearful face potentiates the effects of exogenous (involuntary, stimulus-driven) attention on performance. Internal states such as trait anxiety can also modulate the impact of attention on early visual processing. However, attention does not only improve performance; it also alters the way visual information appears to us, e.g. by enhancing perceived contrast. Here we show that emotion potentiates the effects of exogenous attention on both performance and perceived contrast. Moreover, we found that trait anxiety mediates these effects, with stronger influences of attention and emotion in anxious observers. Finally, changes in performance and appearance correlated with each other, likely reflecting common attentional modulations. Altogether, our findings show that emotion and anxiety interact with selective attention to truly alter how we see.
Small de novo CNVs as biomarkers of parental exposure to low doses of ionizing radiation of caesium-137
Authors: Costa Emília Oliveira Alves , Pinto Irene Plaza , Gonçalves Macks Wendhell , da Silva Juliana Ferreira , Oliveira Lorraynne Guimarães , da Cruz Alex Silva , Silva Daniela de Melo e , da Silva Cláudio Carlos , Pereira Rinaldo Wellerson , da Cruz Aparecido Divino
Published: April 2018

The radiological accident in Goiania in 1987 caused a trail of human contamination, animal, plant and environmental by a radionuclide. Exposure to ionizing radiation results in different types of DNA lesions. The mutagenic effects of ionizing radiation on the germline are special concern because they can endures for several generations, leading to an increase in the rate of mutations in children of irradiated parents. Thus, to evaluate the biological mechanisms of ionizing radiation in somatic and germline cells, with consequent determination of the rate mutations, is extremely important for the estimation of genetic risks. Recently it was established that Chromosomal Microarray Analysis is an important tool for detecting wide spectra of gains or losses in the human genome. Here we present the results of the effect of accidental exposure to low doses of ionizing radiation on the formation of CNVs in the progeny of a human population accidentally exposed to Caesium-137 during the radiological accident in Goiânia, Brazil.
In-situ, In-Memory Stateful Vector Logic Operations based on Voltage Controlled Magnetic Anisotropy
Authors: Jaiswal Akhilesh , Agrawal Amogh , Roy Kaushik
Published: April 2018

Recently, the exponential increase in compute requirements demanded by emerging applications like artificial intelligence, Internet of things, etc. have rendered the state-of-art von-Neumann machines inefficient in terms of energy and throughput owing to the well-known von-Neumann bottleneck. A promising approach to mitigate the bottleneck is to do computations as close to the memory units as possible. One extreme possibility is to do in-situ Boolean logic computations by using stateful devices. Stateful devices are those that can act both as a compute engine and storage device, simultaneously. We propose such stateful, vector, in-memory operations using voltage controlled magnetic anisotropy (VCMA) effect in magnetic tunnel junctions (MTJ). Our proposal is based on the well known manufacturable 1-transistor - 1-MTJ bit-cell and does not require any modifications in the bit-cell circuit or the magnetic device. Instead, we leverage the very physics of the VCMA effect to enable stateful computations. Specifically, we exploit the voltage asymmetry of the VCMA effect to construct stateful IMP (implication) gate and use the precessional switching dynamics of the VCMA devices to propose a massively parallel NOT operation. Further, we show that other gates like AND, OR, NAND, NOR, NIMP (complement of implication) can be implemented using multi-cycle operations.
Gestational exposure to metformin programs improved glucose tolerance and insulin secretion in adult male mouse offspring
Authors: Gregg Brigid E. , Botezatu Nathalie , Brill Joshua D. , Hafner Hannah , Vadrevu Suryakiran , Satin Leslie S. , Alejandro Emilyn U. , Bernal-Mizrachi Ernesto
Published: April 2018

Pancreatic β-cells are exquisitely sensitive to developmental nutrient stressors, and alterations in nutrient sensing pathways may underlie changes observed in these models. Here we developed a mouse model of in utero exposure to the anti-diabetic agent metformin. We have previously shown that this exposure increases offspring pancreatic β-cell mass at birth. We hypothesized that adult offspring would have improved metabolic parameters as a long-term outcome of metformin exposure. Virgin dams were given 5 mg/mL metformin in their water from E0.5 to delivery at E18.5. Body weight, glucose tolerance, insulin tolerance and glucose stimulated insulin secretion were analyzed in the offspring. When male offspring of dams given metformin during gestation were tested as adults they had improved glucose tolerance and enhanced insulin secretion in vivo as did their islets in vitro. Enhanced insulin secretion was accompanied by changes in intracellular free calcium responses to glucose and potassium chloride, possibly mediated by increased L channel expression. Female offspring exhibited improved glucose tolerance at advanced ages. In conclusion, in this model in utero metformin exposure leads to improved offspring metabolism in a gender-specific manner. These findings suggest that metformin applied during gestation may be an option for reprogramming metabolism in at risk groups.
Effect of Nb concentration on the spin-orbit coupling strength in Nb-doped SrTiO3 epitaxial thin films
Authors: Cho Seong Won , Lee Milim , Woo Sungmin , Yim Kanghoon , Han Seungwu , Choi Woo Seok , Lee Suyoun
Published: April 2018

Several oxide materials have attracted much interest for the application in spintronic devices due to unusual properties originating from the strongly correlated orbital and spin degrees of freedom. One missing part in oxide spintronics is a good spin channel featured by strong spin-orbit coupling (SOC) which enables an efficient control of the electron’s spin. We have systematically investigated the dependence of the SOC strength of Sr(Nb
x
Ti1−x)O3 thin films on Nb concentration (nNb = 2~20 at. %) as a deeper exploration of a recent finding of the strong SOC in a heavily Nb-doped SrTiO3 (Sr(Nb0.2Ti0.8)O3) epitaxial film. Apart from a finding of a proportionality of the SOC to nNb, we have observed an intriguing temperature dependence of the SOC strength and the anisotropic magnetoresistance (MR) in the intermediate nNb region. These phenomena are associated with the temperature dependence of Landé g-factor and the change of the band structure, which is consistent with the result of density functional theory (DFT) calculation.
A large-scale survey of the postmortem human microbiome, and its potential to provide insight into the living health condition
Authors: Pechal Jennifer L. , Schmidt Carl J. , Jordan Heather R. , Benbow M. Eric
Published: April 2018

The microbiome plays many roles in human health, often through the exclusive lens of clinical interest. The inevitable end point for all living hosts, death, has its own altered microbiome configurations. However, little is understood about the ecology and changes of microbial communities after death, or their potential utility for understanding the health condition of the recently living. Here we reveal distinct postmortem microbiomes of human hosts from a large-scale survey of death cases representing a predominantly urban population, and demonstrated these microbiomes reflected antemortem health conditions within 24–48 hours of death. Our results characterized microbial community structure and predicted function from 188 cases representing a cross-section of an industrial-urban population. We found strong niche differentiation of anatomic habitat and microbial community turnover based on topographical distribution. Microbial community stability was documented up to two days after death. Additionally, we observed a positive relationship between cell motility and time since host death. Interestingly, we discovered evidence that microbial biodiversity is a predictor of antemortem host health condition (e.g., heart disease). These findings improve the understanding of postmortem host microbiota dynamics, and provide a robust dataset to test the postmortem microbiome as a tool for assessing health conditions in living populations.
Fluorinated reduced graphene oxide as a protective layer on the metallic lithium for application in the high energy batteries
Authors: Bobnar Jernej , Lozinšek Matic , Kapun Gregor , Njel Christian , Dedryvère Rémi , Genorio Boštjan , Dominko Robert
Published: April 2018

Metallic lithium is considered to be one of the most promising anode materials since it offers high volumetric and gravimetric energy densities when combined with high-voltage or high-capacity cathodes. However, the main impediment to the practical applications of metallic lithium is its unstable solid electrolyte interface (SEI), which results in constant lithium consumption for the formation of fresh SEI, together with lithium dendritic growth during electrochemical cycling. Here we present the electrochemical performance of a fluorinated reduced graphene oxide interlayer (FGI) on the metallic lithium surface, tested in lithium symmetrical cells and in combination with two different cathode materials. The FGI on the metallic lithium exhibit two roles, firstly it acts as a Li-ion conductive layer and electronic insulator and secondly, it effectively suppresses the formation of high surface area lithium (HSAL). An enhanced electrochemical performance of the full cell battery system with two different types of cathodes was shown in the carbonate or in the ether based electrolytes. The presented results indicate a potential application in future secondary Li-metal batteries.
ENSO-driven climate variability promotes periodic major outbreaks of dengue in Venezuela
Authors: Vincenti-Gonzalez M. F. , Tami A. , Lizarazo E. F. , Grillet M. E.
Published: April 2018

Dengue is a mosquito-borne viral disease of global impact. In Venezuela, dengue has emerged as one of the most important public health problems of urban areas with frequent epidemics since 2001. The long-term pattern of this disease has involved not only a general upward trend in cases but also a dramatic increase in the size and frequency of epidemic outbreaks. By assuming that climate variability has a relevant influence on these changes in time, we quantified the periodicity of dengue incidence in time-series of data from two northern regions of Venezuela. Disease cycles of 1 and 3–4 years (p < 0.05) were detected. We determined that dengue cycles corresponded with local climate and the El Niño Southern Oscillation (ENSO) variation at both seasonal and inter-annual scales (every 2–3 years). Dengue incidence peaks were more prevalent during the warmer and dryer years of El Niño confirming that ENSO is a regional climatic driver of such long-term periodicity through local changes in temperature and rainfall. Our findings support the evidence of the effect of climate on dengue dynamics and advocate the incorporation of climate information in the surveillance and prediction of this arboviral disease in Venezuela.
ACTH and PMX53 recover synaptic transcriptome alterations in a rat model of infantile spasms
Authors: Iacobaş Dumitru A. , Chachua Tamar , Iacobaş Sanda , Benson Melissa J. , Borges Karin , Velíšková Jana , Velíšek Libor
Published: April 2018

We profiled the gene expression in the hypothalamic arcuate nuclei (ARC) of 20 male and 20 female rats to determine the infantile spasms (IS) related transcriptomic alteration of neurotransmission and recovery following two treatments. Rats were prenatally exposed to betamethasone or saline followed by repeated postnatal subjection to NMDA-triggered IS. Rats with spasms were treated with ACTH, PMX53 or saline. Since ACTH, the first line treatment for IS, has inconsistent efficacy and potential harsh side effects, PMX53, a potent complement C5ar1 antagonist, was suggested as a therapeutic alternative given its effects in other epilepsy models. Novel measures that consider all genes and are not affected by arbitrary cut-offs were used, in addition to standard statistical tests, to quantify regulation and recovery of glutamatergic, GABAergic, cholinergic, dopaminergic and serotonergic pathways. Although IS alters expression of ~30% of the ARC genes in both sexes the transcriptomic effects are 3× more severe in males than their female counterparts, as indicated by the Weighted Pathway Regulation measure. Both treatments significantly restored the ARC neurotransmission transcriptome to the non-IS condition with PMX53 performing slightly better, as measured by the Pathway Restoration Efficiency, suggesting these treatments may reduce autistic traits often associated with IS.
Effects of different doses of granulocyte colony-stimulating factor mobilization therapy on ischemic cardiomyopathy
Authors: Huang Rongchong , Lv Haichen , Yao Kang , Ge Lei , Ye Zhishuai , Ding Huaiyu , Zhang Yiqi , Lu Hao , Huang Zheyong , Zhang Shuning , Zou Yunzeng , Ge Junbo
Published: April 2018

G-CSF mobilization might be beneficial to ICM, but the relationship between effect/safety and the dosage of G-CSF remains unclear. In this study, 24 pigs were used to build ICM models and were randomized into four groups. Four weeks later, different dosages of G-CSF were given daily by subcutaneous injection for 5 days. Another 4 weeks later, all the animals were sacrificed. Electrocardiography, coronary arteriography, left ventriculography, transthoracic echocardiography, cardiac MRI, and SPECT, histopathologic analysis, and immunohistochemistry techniques were used to evaluate left ventricular function and myocardial infarct size. Four weeks after G-CSF treatment, pigs in middle-dose G-CSF group exhibited obvious improvements of left ventricular remodeling and function. Moderate G-CSF mobilization ameliorated the regional contractility of ICM, preserved myocardial viability, and reduced myocardial infarct size. More neovascularization and fewer apoptotic myocardial cells were observed in the ischemic region of the heart in middle-dose group. Expression of vWF, VEGF and MCP-1 were up-regulated, and Akt1 was activated in high- and middle-dose groups. Moreover, CRP, TNF-α and S-100 were elevated after high-dose G-CSF mobilization. Middle-dose G-CSF mobilization therapy is an effective and safe treatment for ICM, and probably acts via a mechanism involving promoting neovascularization, inhibiting cardiac fibrosis and anti-apoptosis.
Trends in the Timing and Magnitude of Ice-Jam Floods in Canada
Authors: Rokaya Prabin , Budhathoki Sujata , Lindenschmidt Karl-Erich
Published: April 2018

Ice-jam floods (IJFs) are important hydrological and hydraulic events in the northern hemisphere that are of major concern for citizens, authorities, insurance companies and government agencies. In recent years, there have been advances in assessing and quantifying climate change impacts on river ice processes, however, an understanding of climate change and regulation impacts on the timing and magnitude of IJFs remains limited. This study presents a global overview of IJF case studies and discusses IJF risks in North America, one of the most IJF prone regions according to literature. Then an assessment of shifts in the timing and magnitude of IJFs in Canada is presented analyzing flow data from 1107 hydrometric stations across Canada for the period from 1903 to 2015. The analyses show clear signals of climate change and regulation impacts in the timing and magnitude of IJFs, particularly in small basins.
Yeast aconitase mitochondrial import is modulated by interactions of its C and N terminal domains and Ssa1/2 (Hsp70)
Authors: Ben-Menachem Reut , Wang Katherine , Marcu Orly , Yu Zhang , Lim Teck Kwang , Lin Qingsong , Schueler- Furman Ora , Pines Ophry
Published: April 2018

Molecules of single proteins, echoforms, can be distributed between two (or more) subcellular locations, a phenomenon which we refer to as dual targeting or dual localization. The yeast aconitase gene ACO1 (778 amino acids), encodes a single translation product that is nonetheless dual localized to the cytosol and mitochondria by a reverse translocation mechanism. The solved crystal structure of aconitase isolated from porcine heart mitochondria shows that it has four domains. The first three tightly associated N-terminal domains are tethered to the larger C-terminal fourth domain (C-terminal amino acids 517–778). We have previously shown that the aconitase C terminal domain constitutes an independent dual targeting signal when fused to mitochondria-targeted passenger-proteins. We show that the aconitase N and C-terminal domains interact and that this interaction is important for efficient aconitase post translational import into mitochondria and for aconitase dual targeting (relative levels of aconitase echoforms). Our results suggest a “chaperone-like function” of the C terminal domain towards the N terminal domains which can be modulated by Ssa1/2 (cytosolic Hsp70).
Catalytically active inclusion bodies of L-lysine decarboxylase from E. coli for 1,5-diaminopentane production
Authors: Kloss Ramona , Limberg Michael H. , Mackfeld Ursula , Hahn Doris , Grünberger Alexander , Jäger Vera D. , Krauss Ulrich , Oldiges Marco , Pohl Martina
Published: April 2018

Sustainable and eco-efficient alternatives for the production of platform chemicals, fuels and chemical building blocks require the development of stable, reusable and recyclable biocatalysts. Here we present a novel concept for the biocatalytic production of 1,5-diaminopentane (DAP, trivial name: cadaverine) using catalytically active inclusion bodies (CatIBs) of the constitutive L-lysine decarboxylase from E. coli (EcLDCc-CatIBs) to process L-lysine-containing culture supernatants from Corynebacterium glutamicum. EcLDCc-CatIBs can easily be produced in E. coli followed by a simple purification protocol yielding up to 43% dry CatIBs per dry cell weight. The stability and recyclability of EcLDCc-CatIBs was demonstrated in (repetitive) batch experiments starting from L-lysine concentrations of 0.1 M and 1 M. EcLDC-CatIBs exhibited great stability under reaction conditions with an estimated half-life of about 54 h. High conversions to DAP of 87–100% were obtained in 30–60 ml batch reactions using approx. 180–300 mg EcLDCc-CatIBs, respectively. This resulted in DAP titres of up to 88.4 g l−1 and space-time yields of up to 660 gDAP l−1 d−1 per gram dry EcLDCc-CatIBs. The new process for DAP production can therefore compete with the currently best fermentative process as described in the literature.
Efficient differentiation of cardiomyocytes and generation of calcium-sensor reporter lines from nonhuman primate iPSCs
Authors: Lin Yongshun , Liu Huimin , Klein Michael , Ostrominski John , Hong So Gun , Yada Ravi Chandra , Chen Guibin , Navarengom Keron , Schwartzbeck Robin , San Hong , Yu Zu-Xi , Liu Chengyu , Linask Kaari , Beers Jeanette , Qiu Lugui , Dunbar Cynthia E. , Boehm Manfred , Zou Jizhong
Published: April 2018

Nonhuman primate (NHP) models are more predictive than rodent models for developing induced pluripotent stem cell (iPSC)-based cell therapy, but robust and reproducible NHP iPSC-cardiomyocyte differentiation protocols are lacking for cardiomyopathies research. We developed a method to differentiate integration-free rhesus macaque iPSCs (RhiPSCs) into cardiomyocytes with >85% purity in 10 days, using fully chemically defined conditions. To enable visualization of intracellular calcium flux in beating cardiomyocytes, we used CRISPR/Cas9 to stably knock-in genetically encoded calcium indicators at the rhesus AAVS1 safe harbor locus. Rhesus cardiomyocytes derived by our stepwise differentiation method express signature cardiac markers and show normal electrochemical coupling. They are responsive to cardiorelevant drugs and can be successfully engrafted in a mouse myocardial infarction model. Our approach provides a powerful tool for generation of NHP iPSC-derived cardiomyocytes amenable to utilization in basic research and preclinical studies, including in vivo tissue regeneration models and drug screening.
GADD45A and CDKN1A are involved in apoptosis and cell cycle modulatory effects of viscumTT with further inactivation of the STAT3 pathway
Authors: Kleinsimon Susann , Longmuss Enya , Rolff Jana , Jäger Sebastian , Eggert Angelika , Delebinski Catharina , Seifert Georg
Published: April 2018

ViscumTT, a whole mistletoe preparation, has shown synergistic induction of apoptosis in several pediatric tumor entities. High therapeutic potential has previously been observed in Ewing’s sarcoma, rhabdomyosarcoma, ALL and AML. In this study, we analyzed modulatory effects on the cell cycle by viscumTT in three osteosarcoma cell lines with various TP53 statuses. ViscumTT treatment induced G1 arrest in TP53 wild-type and null-mutant cells, but S arrest in TP53 mutant cells. Blockage of G1/S transition was accompanied by down-regulation of the key regulators CDK4, CCND1, CDK2, CCNE, CCNA. However, investigations on the transcriptional level revealed secondary TP53 participation. Cell cycle arrest was predominantly mediated by transcriptionally increased expression of GADD45A and CDKN1A and decreased SKP2 levels. Enhanced CDKN1A and GADD45A expression further played a role in viscumTT-induced apoptosis with involvement of stress-induced MAPK8 and inactivation of MAPK1/3. Furthermore, viscumTT inhibited the pro-survival pathway STAT3 by dephosphorylation of the two sites, Tyr705 and Ser727, by down-regulation of total STAT3 and its direct downstream targets BIRC5 and C-MYC. Moreover, tests of the efficacy of viscumTT in vivo showing reduction of tumor volume confirmed the high therapeutic potential as an anti-tumoral agent for osteosarcoma.
Author Correction: Coherent scatter-controlled phase-change grating structures in silicon using femtosecond laser pulses
Authors: Fuentes-Edfuf Yasser , Garcia-Lechuga Mario , Puerto Daniel , Florian Camilo , Garcia-Leis Adianez , Sanchez-Cortes Santiago , Solis Javier , Siegel Jan
Published: April 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Author Correction: EEG Transients in the Sigma Range During non-REM Sleep Predict Learning in Dogs
Authors: Iotchev Ivaylo Borislavov , Kis Anna , Bódizs Róbert , van Luijtelaar Gilles , Kubinyi Enikő
Published: April 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Author Correction: Methods for Scarless, Selection-Free Generation of Human Cells and Allele-Specific Functional Analysis of Disease-Associated SNPs and Variants of Uncertain Significance
Authors: Coggins Nicole B. , Stultz Jacob , O’Geen Henriette , Carvajal-Carmona Luis G. , Segal David J.
Published: April 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Publisher Correction: Shedding light on the neonatal brain: probing cerebral hemodynamics by diffuse optical spectroscopic methods
Authors: Farzam Parisa , Buckley Erin M. , Lin Pei-Yi , Hagan Katherine , Grant P. Ellen , Inder Terrie Eleanor , Carp Stefan A. , Franceschini Maria Angela
Published: April 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Understanding physical (in-) activity, overweight, and obesity in childhood: Effects of congruence between physical self-concept and motor competence
Authors: Utesch T. , Dreiskämper D. , Naul R. , Geukes K.
Published: April 2018

Both the physical self-concept and actual motor competence are important for healthy future physical activity levels and consequently decrease overweight and obesity in childhood. However, children scoring high on motor competence do not necessarily report high levels of physical self-concept and vice versa, resulting in respective (in-) accuracy also referred to as (non-) veridicality. This study examines whether children’s accuracy of physical self-concept is a meaningful predictive factor for their future physical activity. Motor competence, physical self-concept and physical activity were assessed in 3rd grade and one year later in 4th grade. Children’s weight status was categorized based on WHO recommendations. Polynomial regression with Response surface analyses were conducted with a quasi-DIF approach examining moderating weight status effects. Analyses revealed that children with higher motor competence levels and higher self-perceptions show greater physical activity. Importantly, children who perceive their motor competence more accurately (compared to less) show more future physical activity. This effect is strong for underweight and overweight/obese children, but weak for normal weight children. This study indicates that an accurate self-perception of motor competence fosters future physical activity beyond single main effects, respectively. Hence, the promotion of actual motor competence should be linked with the respective development of accurate self-knowledge.