bluuebunny/crossref_metadata_2025 huggingface dataset:
Epigenome-wide DNA methylation profiling in Progressive Supranuclear Palsy reveals major changes at DLX1
Authors: Weber Axel , Schwarz Sigrid C. , Tost Jörg , Trümbach Dietrich , Winter Pia , Busato Florence , Tacik Pawel , Windhorst Anita C. , Fagny Maud , Arzberger Thomas , McLean Catriona , van Swieten John C. , Schwarz Johannes , Vogt Weisenhorn Daniela , Wurst Wolfgang , Adhikary Till , Dickson Dennis W. , Höglinger Günter U. , Müller Ulrich
Published: July 2018

Genetic, epigenetic, and environmental factors contribute to the multifactorial disorder progressive supranuclear palsy (PSP). Here, we study epigenetic changes by genome-wide analysis of DNA from postmortem tissue of forebrains of patients and controls and detect significant (P < 0.05) methylation differences at 717 CpG sites in PSP vs. controls. Four-hundred fifty-one of these sites are associated with protein-coding genes. While differential methylation only affects a few sites in most genes,DLX1is hypermethylated at multiple sites. Expression of an antisense transcript ofDLX1,DLX1AS, is reduced in PSP brains. The amount of DLX1 protein is increased in gray matter of PSP forebrains. Pathway analysis suggests that DLX1 influencesMAPT-encoded Tau protein. In a cell system, overexpression ofDLX1results in downregulation ofMAPTwhile overexpression ofDLX1AScauses upregulation ofMAPT. Our observations suggest that alteredDLX1methylation and expression contribute to pathogenesis of PSP by influencingMAPT.
Pause sequences facilitate entry into long-lived paused states by reducing RNA polymerase transcription rates
Authors: Gabizon Ronen , Lee Antony , Vahedian-Movahed Hanif , Ebright Richard H. , Bustamante Carlos J.
Published: July 2018

Transcription by RNA polymerase (RNAP) is interspersed with sequence-dependent pausing. The processes through which paused states are accessed and stabilized occur at spatiotemporal scales beyond the resolution of previous methods, and are poorly understood. Here, we combine high-resolution optical trapping with improved data analysis methods to investigate the formation of paused states at enhanced temporal resolution. We find that pause sites reduce the forward transcription rate of nearly all RNAP molecules, rather than just affecting the subset of molecules that enter long-lived pauses. We propose that the reduced rates at pause sites allow time for the elongation complex to undergo conformational changes required to enter long-lived pauses. We also find that backtracking occurs stepwise, with states backtracked by at most one base pair forming quickly, and further backtracking occurring slowly. Finally, we find that nascent RNA structures act as modulators that either enhance or attenuate pausing, depending on the sequence context.
Concerted ESCRT and clathrin recruitment waves define the timing and morphology of intraluminal vesicle formation
Authors: Wenzel Eva Maria , Schultz Sebastian Wolfgang , Schink Kay Oliver , Pedersen Nina Marie , Nähse Viola , Carlson Andreas , Brech Andreas , Stenmark Harald , Raiborg Camilla
Published: July 2018

The endosomal sorting complex required for transport (ESCRT) machinery mediates cargo sorting, membrane deformation and membrane scission on the surface of endosomes, generating intraluminal vesicles (ILVs) to degrade signaling receptors. By live-cell imaging of individual endosomes in human cells, we find that ESCRT proteins are recruited in a repetitive pattern: ESCRT-0 and -I show a gradual and linear recruitment and dissociation, whereas ESCRT-III and its regulatory ATPase VPS4 display fast and transient dynamics. Electron microscopy shows that ILVs are formed consecutively, starting immediately after endocytic uptake of cargo proteins and correlating with the repeated ESCRT recruitment waves, unraveling the timing of ILV formation. Clathrin, recruited by ESCRT-0, is required for timely ESCRT-0 dissociation, efficient ILV formation, correct ILV size and cargo degradation. Thus, cargo sorting and ILV formation occur by concerted, coordinated and repetitive recruitment waves of individual ESCRT subcomplexes and are controlled by clathrin.
Immediate hydroxylation of arenes to phenols via V-containing all-silica ZSM-22 zeolite triggered non-radical mechanism
Authors: Zhou Yu , Ma Zhipan , Tang Junjie , Yan Ning , Du Yonghua , Xi Shibo , Wang Kai , Zhang Wei , Wen Haimeng , Wang Jun
Published: July 2018

Hydroxylation of arenes via activation of aromatic Csp2–H bond has attracted great attention for decades but remains a huge challenge. Herein, we achieve the ring hydroxylation of various arenes with stoichiometric hydrogen peroxide (H2O2) into the corresponding phenols on a robust heterogeneous catalyst series of V–Si–ZSM-22 (TON type vanadium silicalite zeolites) that is straightforward synthesized from an unusual ionic liquid involved dry-gel-conversion route. For benzene hydroxylation, the phenol yield is 30.8% (selectivity >99%). Ring hydroxylation of mono-/di-alkylbenzenes and halogenated aromatic hydrocarbons cause the yields up to 26.2% and selectivities above 90%. The reaction is completed within 30 s, the fastest occasion so far, resulting in ultra-high turnover frequencies (TOFs). Systematic characterization including 51V NMR and X-ray absorption fine structure (XAFS) analyses suggest that such high activity associates with the unique non-radical hydroxylation mechanism arising from the in situ created diperoxo V(IV) state.
Mechanical mismatch-driven rippling in carbon-coated silicon sheets for stress-resilient battery anodes
Authors: Ryu Jaegeon , Chen Tianwu , Bok Taesoo , Song Gyujin , Ma Jiyoung , Hwang Chihyun , Luo Langli , Song Hyun-Kon , Cho Jaephil , Wang Chongmin , Zhang Sulin , Park Soojin
Published: July 2018

High-theoretical capacity and low working potential make silicon ideal anode for lithium ion batteries. However, the large volume change of silicon upon lithiation/delithiation poses a critical challenge for stable battery operations. Here, we introduce an unprecedented design, which takes advantage of large deformation and ensures the structural stability of the material by developing a two-dimensional silicon nanosheet coated with a thin carbon layer. During electrochemical cycling, this carbon coated silicon nanosheet exhibits unique deformation patterns, featuring accommodation of deformation in the thickness direction upon lithiation, while forming ripples upon delithiation, as demonstrated by in situ transmission electron microscopy observation and chemomechanical simulation. The ripple formation presents a unique mechanism for releasing the cycling induced stress, rendering the electrode much more stable and durable than the uncoated counterparts. This work demonstrates a general principle as how to take the advantage of the large deformation materials for designing high capacity electrode.
Exome sequencing for paediatric-onset diseases: impact of the extensive involvement of medical geneticists in the diagnostic odyssey
Authors: Mak Christopher CY , Leung Gordon KC , Mok Gary TK , Yeung Kit San , Yang Wanling , Fung Cheuk-Wing , Chan Sophelia HS , Lee So-Lun , Lee Ni-Chung , Pfundt Rolph , Lau Yu-Lung , Chung Brian HY
Published: July 2018

Currently, offering whole-exome sequencing (WES) via collaboration with an external laboratory is increasingly common. However, the receipt of a WES report can be merely the beginning of a continuing exploration process rather than the end of the diagnostic odyssey. The laboratory often does not have the information the physician has, and any discrepancies in variant interpretation must be addressed by a medical geneticist. In this study, we performed diagnostic WES of 104 patients with paediatric-onset genetic diseases. The post-exome review of WES reports by the clinical geneticist led to a more comprehensive assessment of variant pathogenicity in 16 cases. The overall diagnostic yield was 41% (n = 43). Among these 43 diagnoses, 51% (22/43) of the pathogenic variants were nucleotide changes that have not been previously reported. The time required for the post-exome review of the WES reports varied, and 26% (n = 27) of the reports required an extensive amount of time (>3 h) for the geneticist to review. In this predominantly Chinese cohort, we highlight the importance of discrepancies between global and ethnic-specific frequencies of a genetic variant that complicate variant interpretation and the significance of post-exome diagnostic modalities in genetic diagnosis using WES. The challenges faced by geneticists in interpreting WES reports are also discussed.
NASA’s Cold Atom Lab (CAL): system development and ground test status
Authors: Elliott Ethan R. , Krutzik Markus C. , Williams Jason R. , Thompson Robert J. , Aveline David C.
Published: July 2018

We report the status of the Cold Atom Lab (CAL) instrument to be operated aboard the International Space Station (ISS). Utilizing a compact atom chip-based system to create ultracold mixtures and degenerate samples of 87Rb, 39K, and 41K, CAL is a multi-user facility developed by NASA’s Jet Propulsion Laboratory to provide the first persistent quantum gas platform in the microgravity conditions of space. Within this unique environment, atom traps can be decompressed to arbitrarily weak confining potentials, producing a new regime of picokelvin temperatures and ultra-low densities. Further, the complete removal of these confining potential allows the free fall evolution of ultracold clouds to be observed on unprecedented timescales compared to earthbound instruments. This unique facility will enable novel ultracold atom research to be remotely performed by an international group of principle investigators with broad applications in fundamental physics and inertial sensing. Here, we describe the development and validation of critical CAL technologies, including demonstration of the first on-chip Bose–Einstein condensation (BEC) of 87Rb with microwave-based evaporation and the generation of ultracold dual-species quantum gas mixtures of 39K/87Rb and 41K/87Rb in an atom chip trap via sympathetic cooling.
Decoding microglia responses to psychosocial stress reveals blood-brain barrier breakdown that may drive stress susceptibility
Authors: Lehmann Michael L. , Weigel Thaddeus K. , Cooper Hannah A. , Elkahloun Abdel G. , Kigar Stacey L. , Herkenham Miles
Published: July 2018

An animal’s ability to cope with or succumb to deleterious effects of chronic psychological stress may be rooted in the brain’s immune responses manifested in microglial activity. Mice subjected to chronic social defeat (CSD) were categorized as susceptible (CSD-S) or resilient (CSD-R) based on behavioral phenotyping, and their microglia were isolated and analyzed by microarray. Microglia transcriptomes from CSD-S mice were enriched for pathways associated with inflammation, phagocytosis, oxidative stress, and extracellular matrix remodeling. Histochemical experiments confirmed the array predictions: CSD-S microglia showed elevated phagocytosis and oxidative stress, and the brains of CSD-S but not CSD-R or non-stressed control mice showed vascular leakage of intravenously injected fluorescent tracers. The results suggest that the inflammatory profile of CSD-S microglia may be precipitated by extracellular matrix degradation, oxidative stress, microbleeds, and entry and phagocytosis of blood-borne substances into brain parenchyma. We hypothesize that these CNS-centric responses contribute to the stress-susceptible behavioral phenotype.
The habu genome reveals accelerated evolution of venom protein genes
Authors: Shibata Hiroki , Chijiwa Takahito , Oda-Ueda Naoko , Nakamura Hitomi , Yamaguchi Kazuaki , Hattori Shousaku , Matsubara Kazumi , Matsuda Yoichi , Yamashita Akifumi , Isomoto Akiko , Mori Kazuki , Tashiro Kosuke , Kuhara Satoru , Yamasaki Shinichi , Fujie Manabu , Goto Hiroki , Koyanagi Ryo , Takeuchi Takeshi , Fukumaki Yasuyuki , Ohno Motonori , Shoguchi Eiichi , Hisata Kanako , Satoh Noriyuki , Ogawa Tomohisa
Published: July 2018

Evolution of novel traits is a challenging subject in biological research. Several snake lineages developed elaborate venom systems to deliver complex protein mixtures for prey capture. To understand mechanisms involved in snake venom evolution, we decoded here the ~1.4-Gb genome of a habu, Protobothrops flavoviridis. We identified 60 snake venom protein genes (SV) and 224 non-venom paralogs (NV), belonging to 18 gene families. Molecular phylogeny reveals early divergence of SV and NV genes, suggesting that one of the four copies generated through two rounds of whole-genome duplication was modified for use as a toxin. Among them, both SV and NV genes in four major components were extensively duplicated after their diversification, but accelerated evolution is evident exclusively in the SV genes. Both venom-related SV and NV genes are significantly enriched in microchromosomes. The present study thus provides a genetic background for evolution of snake venom composition.
The Polynomial Volume Law of Complex Networks in the Context of Local and Global Optimization
Authors: Mocnik Franz-Benjamin
Published: July 2018

Many complex networks expose global hub structures: for some nodes, the number of incident edges far exceeds the average, leading to a small average shortest path length. Such ‘small-world properties’ are often guided by a scale-free power-law distribution of the node degrees, and self-organization inside the network has been identified as a reason driving the emergence of this structure. Small-world networks have recently raised lots of interest, because they capture the global topology of the World-Wide Web, metabolic, and social networks. While small-world networks reflect global structures, little attention is paid to the local structure of complex networks. In this article neighbourhoods are demonstrated to share a common local structure in many real complex networks, manifested by a polynomial volume law. This law can, in case of networks that are embedded in space, be explained in terms of the embedding and the properties of Euclidean space. A model of hierarchical spatial networks is introduced to examine the effect of global structures, in particular of hierarchies, on the polynomial volume law. It turns out that the law is robust against the coexistence of such global structures. The local structure of space and global optimization can both be found in transport, brain, and communication networks, which suggests the polynomial volume law, often in combination with hierarchies or other global optimization principles, to be a generic property inherent to many networks.
Vrk1 partial Knockdown in Mice Results in Reduced Brain Weight and Mild Motor Dysfunction, and Indicates Neuronal VRK1 Target Pathways
Authors: Vinograd-Byk Hadar , Renbaum Paul , Levy-Lahad Ephrat
Published: July 2018

Mutations in Vaccinia-related kinase 1 (VRK1) have emerged as a cause of severe neuronal phenotypes in human, including brain developmental defects and degeneration of spinal motor neurons, leading to Spinal Muscular Atrophy (SMA) or early onset Amyotrophic Lateral Sclerosis (ALS). Vrk1 gene-trap partial Knockout (KO) mice (Vrk1GT3/GT3), which express decreased levels of Vrk1, are sterile due to impaired gamete production. Here, we examined whether this mouse model also presents neuronal phenotypes. We found a 20–50% reduction in Vrk1 expression in neuronal tissues of the Vrk1GT3/GT3 mice, leading to mild neuronal phenotypes including significant but small reduction in brain mass and motor (rotarod) impairment. Analysis of gene expression in the Vrk1GT3/GT3 cortex predicts novel roles for VRK1 in neuronal pathways including neurotrophin signaling, axon guidance and pathways implicated in the pathogenesis of ALS. Together, our studies of the partial KO Vrk1 mice reveal that even moderately reduced levels of Vrk1 expression result in minor neurological impairment and indicate new neuronal pathways likely involving VRK1.
Structural brain imaging in Alzheimer’s disease and mild cognitive impairment: biomarker analysis and shared morphometry database
Authors: Ledig Christian , Schuh Andreas , Guerrero Ricardo , Heckemann Rolf A. , Rueckert Daniel
Published: July 2018

Magnetic resonance (MR) imaging is a powerful technique for non-invasive in-vivo imaging of the human brain. We employed a recently validated method for robust cross-sectional and longitudinal segmentation of MR brain images from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. Specifically, we segmented 5074 MR brain images into 138 anatomical regions and extracted time-point specific structural volumes and volume change during follow-up intervals of 12 or 24 months. We assessed the extracted biomarkers by determining their power to predict diagnostic classification and by comparing atrophy rates to published meta-studies. The approach enables comprehensive analysis of structural changes within the whole brain. The discriminative power of individual biomarkers (volumes/atrophy rates) is on par with results published by other groups. We publish all quality-checked brain masks, structural segmentations, and extracted biomarkers along with this article. We further share the methodology for brain extraction (pincram) and segmentation (MALPEM, MALPEM4D) as open source projects with the community. The identified biomarkers hold great potential for deeper analysis, and the validated methodology can readily be applied to other imaging cohorts.
Involvement of median preoptic nucleus and medullary noradrenergic neurons in cardiovascular and sympathetic responses of hemorrhagic rats
Authors: Naves Lara Marques , Marques Stefanne Madalena , Mourão Aline Andrade , Fajemiroye James Oluwagbamigbe , Xavier Carlos Henrique , de Castro Carlos Henrique , Rebelo Ana Cristina Silva , Rosa Daniel Alves , Gomes Rodrigo Mello , Colombari Eduardo , Pedrino Gustavo Rodrigues
Published: July 2018

The infusion of hypertonic saline solution (HSS) is known to be beneficial to the treatment of hypovolemic hemorrhage (HH). The central mechanism of HSS-induced cardiovascular and autonomic recovery of animals subjected to HH remains unclear. Hence, the present study evaluated the involvement of median preoptic nucleus (MnPO) and medullary noradrenergic neurons (A1 and A2) in HSS-induced cardiovascular and sympathetic responses in hemorrhagic rats. The wistar rats were subjected to specific lesion of noradrenergic neurons through the nanoinjections of anti-DβH-saporin into caudal ventrolateral medulla (A1 neurons) and nucleus of the solitary tract (A2 neurons). After recovery, mean arterial pressure (MAP) and renal sympathetic nervous activity were recorded. The HH was performed through blood withdrawal until a MAP of 60 mmHg was attained. In sham rats, HSS infusion (3M NaCl) reestablished MAP without change in HH-induced sympathoinhibition. The muscimol (agonist of GABAA receptor) was nanoinjected in MnPO during HH and MnPO inhibition abolished the recovery of MAP and HSS-induced sympathoinhibition. Simultaneous lesions of A1 and A2 abolished MAP restoration and sympathoinhibition after HSS infusion. These results suggest that the recovery of MAP and HSS-induced sympathoinhibition in hemorrhaged rats depend on intact neural projections from A1 and A2 to MnPO.
Computational Design of Epitope-Enriched HIV-1 Gag Antigens with Preserved Structure and Function for Induction of Broad CD8+ T Cell Responses
Authors: Asbach Benedikt , Meier Johannes P. , Pfeifer Matthias , Köstler Josef , Wagner Ralf
Published: July 2018

The partially protective phenotype observed in HIV-infected long-term-non-progressors is often associated with certain HLA alleles, thus indicating that cytotoxic T lymphocyte (CTL) responses play a crucial role in combating virus replication. However, both the vast variability of HIV and the HLA diversity impose a challenge on elicitation of broad and effective CTL responses. Therefore, we conceived an algorithm for the enrichment of CD8+T cell epitopes in HIV’s Gag protein, respecting functional preservation to enable cross-presentation. Experimentally identified epitopes were compared to a Gag reference sequence. Amino-acid-substitutions (AAS) were assessed for their impact on Gag’s budding-function using a trained classifier that considers structural models and sequence conservation. Experimental assessment of Gag-variants harboring selected AAS demonstrated an apparent classifier-precision of 100%. Compatible epitopes were assigned an immunological score that incorporates features such as conservation or HLA-association in a user-defined weighted manner. Using a genetic algorithm, the epitopes were incorporated in an iterative manner into novel T-cell-epitope-enriched Gag sequences (TeeGag). Computational evaluation showed that these antigen candidates harbor a higher fraction of epitopes with higher score as compared to natural Gag isolates and other artificial antigen designs. Thus, these designer sequences qualify as next-generation antigen candidates for induction of broader CTL responses.
Prognostication and Risk Factors for Cystic Fibrosis via Automated Machine Learning
Authors: Alaa Ahmed M. , van der Schaar Mihaela
Published: July 2018

Accurate prediction of survival for cystic fibrosis (CF) patients is instrumental in establishing the optimal timing for referring patients with terminal respiratory failure for lung transplantation (LT). Current practice considers referring patients for LT evaluation once the forced expiratory volume (FEV1) drops below 30% of its predicted nominal value. While FEV1 is indeed a strong predictor of CF-related mortality, we hypothesized that the survival behavior of CF patients exhibits a lot more heterogeneity. To this end, we developed an algorithmic framework, which we call AutoPrognosis, that leverages the power of machine learning to automate the process of constructing clinical prognostic models, and used it to build a prognostic model for CF using data from a contemporary cohort that involved 99% of the CF population in the UK. AutoPrognosis uses Bayesian optimization techniques to automate the process of configuring ensembles of machine learning pipelines, which involve imputation, feature processing, classification and calibration algorithms. Because it is automated, it can be used by clinical researchers to build prognostic models without the need for in-depth knowledge of machine learning. Our experiments revealed that the accuracy of the model learned by AutoPrognosis is superior to that of existing guidelines and other competing models.
Statistical modelling of navigational decisions based on intensity versus directionality in Drosophila larval phototaxis
Authors: de Andres-Bragado Lucia , Mazza Christian , Senn Walter , Sprecher Simon G.
Published: July 2018

Organisms use environmental cues for directed navigation. Understanding the basic logic behind navigational decisions critically depends on the complexity of the nervous system. Due to the comparably simple organization of the nervous system of the fruit fly larva, it stands as a powerful model to study decision-making processes that underlie directed navigation. We have quantitatively measured phototaxis in response to well-defined sensory inputs. Subsequently, we have formulated a statistical stochastic model based on biased Markov chains to characterize the behavioural basis of negative phototaxis. Our experiments show that larvae make navigational decisions depending on two independent physical variables: light intensity and its spatial gradient. Furthermore, our statistical model quantifies how larvae balance two potentially-contradictory factors: minimizing exposure to light intensity and at the same time maximizing their distance to the light source. We find that the response to the light field is manifestly non-linear, and saturates above an intensity threshold. The model has been validated against our experimental biological data yielding insight into the strategy that larvae use to achieve their goal with respect to the navigational cue of light, an important piece of information for future work to study the role of the different neuronal components in larval phototaxis.
Investigation on Anti-Autofluorescence, Osteogenesis and Long-Term Tracking of HA-Based Upconversion Material
Authors: Li Xiyu , Zou Qin , Li Wei , Chen Haifeng
Published: July 2018

Hydroxyapatite (HA) material will be long-standing once implanted in bone tissue of the body. It should be considered to endow the osteogenic HA material with traceable fluorescence to realize a lifelong in vivo tracking. We prepared and utilized lanthanides-doped HA upconversion material, and revealed for the first time that the lanthanides (ytterbium (Yb) and holmium (Ho)) co-doped HA upconversion material was suitable for long-term or lifelong in vivo tracking, the lanthanide ions doped in the HA matrix would not affect the biocompatibility and osteogenesis, and the tissue autofluorescence could be effectively avoided by the HA:Yb/Ho upconversion material. Also the distribution in bone and osteointegration with bone of the HA:Yb/Ho material could be clearly discriminated by its bright fluorescence under NIR irradiation. The upconversion characteristic of the HA:Yb/Ho material provides a feasibility and promising prospect for lifelong in vivo tracking, and has an advantage in revealing the material-tissue interrelation. The material has important clinical application value in addition to its usefulness for scientific investigation.
Bacterial inactivation by plasma treated water enhanced by reactive nitrogen species
Authors: Shaw Priyanka , Kumar Naresh , Kwak Hyong Sin , Park Ji Hoon , Uhm Han Sup , Bogaerts Annemie , Choi Eun Ha , Attri Pankaj
Published: July 2018

There is a growing body of literature that recognizes the importance of plasma treated water (PTW) for inactivation of microorganism. However, very little attention has been paid to the role of reactive nitrogen species (RNS) in deactivation of bacteria. The aim of this study is to explore the role of RNS in bacterial killing, and to develop a plasma system with increased sterilization efficiency. To increase the concentration of reactive oxygen and nitrogen species (RONS) in solution, we have used vapor systems (DI water/HNO3 at different wt%) combined with plasma using N2 as working gas. The results show that the addition of the vapor system yields higher RONS contents. Furthermore, PTW produced by N2 + 0.5 wt% HNO3 vapor comprises a large amount of both RNS and ROS, while PTW created by N2 + H2O vapor consists of a large amount of ROS, but much less RNS. Interestingly, we observed more deactivation of E. Coli with PTW created by N2 + 0.5 wt% HNO3 vapor plasma as compared to PTW generated by the other plasma systems. This work provides new insight into the role of RNS along with ROS for deactivation of bacteria.
Driven nonlinear nanomechanical resonators as digital signal detectors
Authors: Tadokoro Yukihiro , Tanaka Hiroya , Dykman M. I.
Published: July 2018

Because of their nonlinearity, vibrational modes of resonantly driven nanomechanical systems have coexisting stable states of forced vibrations in a certain range of the amplitude of the driving force. Depending on its phase, which encodes binary information, a signal at the same frequency increases or decreases the force amplitude. The resulting force amplitude can be outside the range of bistability. The values of the mode amplitude differ significantly on the opposite sides of the bistability region. Therefore the mode amplitude is very sensitive to the signal phase. This suggests using a driven mode as a bi-directional bifurcation amplifier, which switches in the opposite directions depending on the signal phase and provides an essentially digital output. We study the operation of the amplifier near the critical point where the width of the bistability region goes to zero and thus the threshold of the signal amplitude is low. We also develop an analytical technique and study the error rate near the threshold. The results apply to a broad range of currently studied systems and extend to micromechanical systems and nonlinear electromagnetic cavities.
Playing with universality classes of Barkhausen avalanches
Authors: Bohn Felipe , Durin Gianfranco , Correa Marcio Assolin , Machado Núbia Ribeiro , Della Pace Rafael Domingues , Chesman Carlos , Sommer Rubem Luis
Published: July 2018

Many systems crackle, from earthquakes and financial markets to Barkhausen effect in ferromagnetic materials. Despite the diversity in essence, the noise emitted in these dynamical systems consists of avalanche-like events with broad range of sizes and durations, characterized by power-law avalanche distributions and typical average avalanche shape that are fingerprints describing the universality class of the underlying avalanche dynamics. Here we focus on the crackling noise in ferromagnets and scrutinize the traditional statistics of Barkhausen avalanches in polycrystalline and amorphous ferromagnetic films having different thicknesses. We show how scaling exponents and average shape of the avalanches evolve with the structural character of the materials and film thickness. We find quantitative agreement between experiment and theoretical predictions of models for the magnetic domain wall dynamics, and then elucidate the universality classes of Barkhausen avalanches in ferromagnetic films. Thereby, we observe for the first time the dimensional crossover in the domain wall dynamics and the outcomes of the interplay between system dimensionality and range of interactions governing the domain wall dynamics on Barkhausen avalanches.
Nuclear Pore Complex Components in the Malaria Parasite Plasmodium berghei
Authors: Kehrer Jessica , Kuss Claudia , Andres-Pons Amparo , Reustle Anna , Dahan Noa , Devos Damien , Kudryashev Mikhail , Beck Martin , Mair Gunnar R. , Frischknecht Friedrich
Published: July 2018

The nuclear pore complex (NPC) is a large macromolecular assembly of around 30 different proteins, so-called nucleoporins (Nups). Embedded in the nuclear envelope the NPC mediates bi-directional exchange between the cytoplasm and the nucleus and plays a role in transcriptional regulation that is poorly understood. NPCs display modular arrangements with an overall structure that is generally conserved among many eukaryotic phyla. However, Nups of yeast or human origin show little primary sequence conservation with those from early-branching protozoans leaving those of the malaria parasite unrecognized. Here we have combined bioinformatic and genetic methods to identify and spatially characterize Nup components in the rodent infecting parasite Plasmodium berghei and identified orthologs from the human malaria parasite P. falciparum, as well as the related apicomplexan parasite Toxoplasma gondii. For the first time we show the localization of selected Nups throughout the P. berghei life cycle. Largely restricted to apicomplexans we identify an extended C-terminal poly-proline extension in SEC13 that is essential for parasite survival and provide high-resolution images of Plasmodium NPCs obtained by cryo electron tomography. Our data provide the basis for full characterization of NPCs in malaria parasites, early branching unicellular eukaryotes with significant impact on human health.
Mediation analysis reveals common mechanisms of RUNX1 point mutations and RUNX1/RUNX1T1 fusions influencing survival of patients with acute myeloid leukemia
Authors: Hornung Roman , Jurinovic Vindi , Batcha Aarif M. N. , Bamopoulos Stefanos A. , Rothenberg-Thurley Maja , Amler Susanne , Sauerland Maria Cristina , Berdel Wolfgang E. , Wörmann Bernhard J. , Bohlander Stefan K. , Braess Jan , Hiddemann Wolfgang , Lehmann Sören , Mareschal Sylvain , Spiekermann Karsten , Metzeler Klaus H. , Herold Tobias , Boulesteix Anne-Laure
Published: July 2018

Alterations of RUNX1 in acute myeloid leukemia (AML) are associated with either a more favorable outcome in the case of the RUNX1/RUNX1T1 fusion or unfavorable prognosis in the case of point mutations. In this project we aimed to identify genes responsible for the observed differences in outcome that are common to both RUNX1 alterations. Analyzing four AML gene expression data sets (n = 1514), a total of 80 patients with RUNX1/RUNX1T1 and 156 patients with point mutations in RUNX1 were compared. Using the statistical tool of mediation analysis we identified the genes CD109, HOPX, and KIAA0125 as candidates for mediator genes. In an analysis of an independent validation cohort, KIAA0125 again showed a significant influence with respect to the impact of the RUNX1/RUNX1T1 fusion. While there were no significant results for the other two genes in this smaller validation cohort, the observed relations linked with mediation effects (i.e., those between alterations, gene expression and survival) were almost without exception as strong as in the main analysis. Our analysis demonstrates that mediation analysis is a powerful tool in the identification of regulative networks in AML subgroups and could be further used to characterize the influence of genetic alterations.
Comparative genomics of Mycobacterium africanum Lineage 5 and Lineage 6 from Ghana suggests distinct ecological niches
Authors: Otchere Isaac Darko , Coscollá Mireia , Sánchez-Busó Leonor , Asante-Poku Adwoa , Brites Daniela , Loiseau Chloe , Meehan Conor , Osei-Wusu Stephen , Forson Audrey , Laryea Clement , Yahayah Abdallah Iddrisu , Baddoo Akosua , Ansa Gloria Akosua , Aboagye Samuel Yaw , Asare Prince , Borrell Sonia , Gehre Florian , Beckert Patrick , Kohl Thomas A. , N’dira Sanoussi , Beisel Christian , Antonio Martin , Niemann Stefan , de Jong Bouke C. , Parkhill Julian , Harris Simon R. , Gagneux Sebastien , Yeboah-Manu Dorothy
Published: July 2018

Mycobacterium africanum (Maf) causes a substantial proportion of human tuberculosis in some countries of West Africa, but little is known on this pathogen. We compared the genomes of 253 Maf clinical isolates from Ghana, including N = 175 Lineage 5 (L5) and N = 78 Lineage 6 (L6). We found that the genomic diversity of L6 was higher than in L5 despite the smaller sample size. Regulatory proteins appeared to evolve neutrally in L5 but under purifying selection in L6. Even though over 90% of the human T cell epitopes were conserved in both lineages, L6 showed a higher ratio of non-synonymous to synonymous single nucleotide variation in these epitopes overall compared to L5. Of the 10% human T cell epitopes that were variable, most carried mutations that were lineage-specific. Our findings indicate that Maf L5 and L6 differ in some of their population genomic characteristics, possibly reflecting different selection pressures linked to distinct ecological niches.
Home-based Rehabilitation With A Novel Digital Biofeedback System versus Conventional In-person Rehabilitation after Total Knee Replacement: a feasibility study
Authors: Correia Fernando Dias , Nogueira André , Magalhães Ivo , Guimarães Joana , Moreira Maria , Barradas Isabel , Teixeira Laetitia , Tulha José , Seabra Rosmaninho , Lains Jorge , Bento Virgilio
Published: July 2018

In-person home-based rehabilitation and telerehabilitation can be as effective as clinic-based rehabilitation after total knee arthroplasty (TKA), but require heavy logistics and are highly dependent on human supervision. New technologies that allow independent home-based rehabilitation without constant human supervision may help solve this problem. This was a single-center, feasibility study comparing a digital biofeedback system that meets these needs against conventional in-person home-based rehabilitation after TKA over an 8-week program. Primary outcome was the change in the Timed Up and Go score between the end of the program and baseline. Fifty-nine patients completed the study (30 experimental group; 29 conventional rehabilitation). The study demonstrated a superiority of the experimental group for all outcomes. Adverse events were similar in both groups. This is the first study to demonstrate that a digital rehabilitation solution can achieve better outcomes than conventional in-person rehabilitation, while less demanding in terms of human resources.
NPM-hMLF1 fusion protein suppresses defects of a Drosophila FTLD model expressing the human FUS gene
Authors: Yamamoto Itaru , Azuma Yumiko , Kushimura Yukie , Yoshida Hideki , Mizuta Ikuko , Mizuno Toshiki , Ueyama Morio , Nagai Yoshitaka , Tokuda Takahiko , Yamaguchi Masamitsu
Published: July 2018

Fused in sarcoma (FUS) was identified as a component of typical inclusions in frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). In FTLD, both nuclear and cytoplasmic inclusions with wild-type FUS exist, while cytoplasmic inclusions with a mutant-form of FUS occur in many ALS cases. These observations imply that FUS plays a role across these two diseases. In this study, we examined the effect of several proteins including molecular chaperons on the aberrant eye morphology phenotype induced by overexpression of wild-type human FUS (hFUS) in Drosophila eye imaginal discs. By screening, we found that the co-expression of nucleophosmin–human myeloid leukemia factor 1 (NPM-hMLF1) fusion protein could suppress the aberrant eye morphology phenotype induced by hFUS. The driving of hFUS expression at 28 °C down-regulated levels of hFUS and endogenous cabeza, a Drosophila homolog of hFUS. The down-regulation was mediated by proteasome dependent degradation. Co-expression of NPM-hMLF1 suppressed this down-regulation. In addition, co-expression of NPM-hMLF1 partially rescued pharate adult lethal phenotype induced by hFUS in motor neurons. These findings with a Drosophila model that mimics FTLD provide clues for the development of novel FTLD therapies.
Magnetic field driven nodal topological superconductivity in monolayer transition metal dichalcogenides
Authors: He Wen-Yu , Zhou Benjamin T. , He James J. , Yuan Noah F. Q. , Zhang Ting , Law K. T.
Published: July 2018

Recently, Ising superconductors that possess in-plane upper critical fields Hc2 much larger than the Pauli limit field are under intense experimental study. Many monolayer or few layer transition metal dichalcogenides are shown to be Ising superconductors. Here we show that in a wide range of experimentally accessible regimes where the in-plane magnetic field is higher than the Pauli limit field but lower than Hc2, a 2H-structure monolayer NbSe2 or similarly TaS2 becomes a nodal topological superconductor. The bulk nodal points appear on the Γ−M lines of the Brillouin zone where the Ising SOC vanishes. The nodal points are connected by Majorana flat bands, and the flat bands are associated with a large number of Majorana zero energy edge modes that induce spin-triplet Cooper pairs. This work demonstrates an experimentally feasible way to realize Majorana fermions in nodal topological superconductor, without any fine-tuning of experimental parameters.
Real-time assessment of food freshness in refrigerators based on a miniaturized electronic nose
Authors: Wang Min , Gao Fan , Wu Qian , Zhang Junyu , Xue Yingying , Wan Hao , Wang Ping
Published: July 2018

A miniaturized electronic nose comprised of a detection module and freshness assessment module, was developed for real-time assessment of food freshness in a refrigerator.
Enhanced healing activity of burn wound infection by a dextran-HA hydrogel enriched with sanguinarine
Authors: Zhu Qiyu , Jiang Ming , Liu Qiang , Yan Shina , Feng Longbao , Lan Yong , Shan Guiqiu , Xue Wei , Guo Rui
Published: July 2018

SA/GMs/Dex-HA hydrogel provides a potential way for infected burn treatment with high-quality and efficient scar inhibition.
Correction: Heparin-induced tau filaments are structurally heterogeneous and differ from Alzheimer's disease filaments
Authors: Fichou Yann , Vigers Michael , Goring Andrew K. , Eschmann Neil A. , Han Songi
Published: July 2018

Correction for ‘Heparin-induced tau filaments are structurally heterogeneous and differ from Alzheimer's disease filaments’ by Yann Fichou et al., Chem. Commun., 2018, 54, 4573–4576.
Correlating cobalt redox couples to photovoltage in the dye-sensitized solar cell
Authors: Chen Kitty Y. , Schauer Phil A. , Patrick Brian O. , Berlinguette Curtis P.
Published: July 2018

Two sets of structurally analogous Co(iii/ii)-based redox mediators were incorporated in the dye-sensitized solar cells and a linear correlation was demonstrated between redox potential and photovoltage.
Synthesis, crystal structures, and magnetic properties of six transition metal phosphonates
Authors: Xu Hailong , Zhou Hong , Feng Lu , Wang Qiaoyun , Chen Rui , Huang Wentao , Wu Xixi
Published: July 2018

Six new complexes have been quantificationally investigated for magnetic properties. There are abundant water molecules existing in the complexes with different aggregation modes.
Hierarchically distributed microstructure design of haptic sensors for personalized fingertip mechanosensational manipulation
Authors: Liao Xinqin , Wang Wensong , Lin Maohua , Li Minghua , Wu Hualin , Zheng Yuanjin
Published: July 2018

Strategies to help reconstruct and restore haptic perception are essential for control of prosthetic limbs and robotic manipulation.
High affinity interactions of Pb2+with synaptotagmin I
Authors: Katti Sachin , Her Bin , Srivastava Atul K. , Taylor Alexander B. , Lockless Steve W. , Igumenova Tatyana I.
Published: July 2018

Pb2+binds C2 domains with high affinity, desensitizes them to Ca2+, and supports their membrane interactions.
Large-scale transfer-free growth of thin graphite films at low temperature for solid diffusion barriers
Authors: Kang Su Hyoung , Kang Sangmin , Park Seong Chae , Park Jong Bo , Jung Youngjin , Hong Byung Hee
Published: July 2018

Amorphous indium–gallium–zinc oxide (a-IGZO) thin-film transistors (TFTs) have been under intense investigation as one of the promising candidates for active matrix flat-panel displays.
Synthesis of 3-cyanomethylated coumarins by a visible-light-mediated direct cyanomethylation of aryl alkynoates
Authors: Zhang Wei , Yang Chen , Pan Yu-Liang , Li Xin , Cheng Jin-Pei
Published: July 2018

A visible-light-promoted, mild, and direct cyanomethylation of aryl alkynoates has been developed.
Correction: A facile and high-yield formation of dipyrrin-boronic acid dyads and triads: a light-harvesting system in the visible region based on the efficient energy transfer
Authors: Yamamura Masaki , Yazaki Shinya , Seki Motofumi , Matsui Yasunori , Ikeda Hiroshi , Nabeshima Tatsuya
Published: July 2018

Correction for ‘A facile and high-yield formation of dipyrrin-boronic acid dyads and triads: a light-harvesting system in the visible region based on the efficient energy transfer’ by Masaki Yamamura et al., Org. Biomol. Chem., 2015, 13, 2574–2581.
Exploiting CH/π interactions in robust supramolecular adhesives
Authors: Yamate Taiki , Fujiwara Takayuki , Yamaguchi Toru , Suzuki Hiroshi , Akazome Motohiro
Published: July 2018

CH/π interactions drive the high adhesion strength and high water and humidity resistances of a supramolecular adhesive.
Aromatic polyesters from biosuccinic acid
Authors: Short Gabriel N. , Nguyen Ha T. H. , Scheurle Patricia I. , Miller Stephen A.
Published: July 2018

Biosuccinic acid, obtainedviasugar fermentation, is cyclodimerized and oxidized to yield building blocks for aromatic polyesters with high glass transition temperatures.
Comparison of the methods for profiling N-glycans—hepatocellular carcinoma serum glycomics study
Authors: Wang Ran , Liu Yufei , Wang Chang , Li Henghui , Liu Xin , Cheng Liming , Zhou Yanhong
Published: July 2018

Monitoring serum glycomics is one of the most important emerging approaches for diagnosis of various cancers, and the majority of previous studies were based on MALDI-MS or HPLC analysis.
Ultrafast nonlinear optical properties and carrier dynamics of silver nanoparticle-decorated ZnO nanowires
Authors: Zhang Ke-Xin , Yao Cheng-Bao , Wen Xing , Li Qiang-Hua , Sun Wen-Jun
Published: July 2018

Silver (Ag) nanoparticle-decorated zinc oxide (ZnO) nanowires (Ag–ZnO) have been successfully synthesized by chemical vapour deposition and the magnetron sputtering method.
Toxic effects of zinc oxide nanoparticles combined with vitamin C and casein phosphopeptides on gastric epithelium cells and the intestinal absorption of mice
Authors: Gu Tianjiao , Yao Chenjie , Zhang Kangkang , Li Chenchen , Ding Lin , Huang Yanan , Wu Minghong , Wang Yanli
Published: July 2018

Vitamin C is more powerful than casein phosphopeptides at controlling the combined toxic effects induced by ZnO NPs on gastric epithelium cells and intestinal absorption in mice.
Time-dependent and Pb-dependent antagonism and synergism towards Vibrio qinghaiensis sp.-Q67 within heavy metal mixtures
Authors: Zhang Jin , Ding Ting-Ting , Dong Xin-Qin , Bian Zhi-Qiang
Published: July 2018

Toxicity interaction has gained much interest in the research of toxicity of mixture pollutants.
Challenges in application of Raman spectroscopy to biology and materials
Authors: Kuhar Nikki , Sil Sanchita , Verma Taru , Umapathy Siva
Published: July 2018

This paper reviews various facets of Raman spectroscopy. This encompasses biomolecule fingerprinting and conformational analysis, discrimination of healthy vs. diseased states, depth-specific information of materials and 3D Raman imaging.
The Suzuki–Miyaura reaction as a tool for modification of phenoxyl-nitroxyl radicals of the 4H-imidazoleN-oxide series
Authors: Ten Yury A. , Salnikov Oleg G. , Amitina Svetlana A. , Stass Dmitri V. , Rybalova Tatyana V. , Kazantsev Maxim S. , Bogomyakov Artem S. , Mostovich Evgeny A. , Mazhukin Dmitrii G.
Published: July 2018

Pd-catalyzed cross-coupling reaction as a tool for modification of hybrid phenoxyl-nitroxides.
Quasi-single-crystalline CoO hexagrams with abundant defects for highly efficient electrocatalytic water oxidation
Authors: Liang Zuozhong , Huang Zhehao , Yuan Haitao , Yang Zhiyuan , Zhang Chaochao , Xu Yang , Zhang Wei , Zheng Haoquan , Cao Rui
Published: July 2018

Defects and structural long-range ordering have been recognized as two crucial characters for advanced electrocatalysts.
Achieving convenient CO2 electroreduction and photovoltage in tandem using potential-insensitive disordered Ag nanoparticles
Authors: Deng Wanyu , Zhang Lei , Dong Hao , Chang Xiaoxia , Wang Tuo , Gong Jinlong
Published: July 2018

This paper describes the rational design of potential insensitive disordered Ag, which could achieve more than 90% faradaic efficiency for CO within a wide voltage range of ∼1.1 V in a photovoltaic-electrochemical systems for CO2 system.
Probing key elements of teixobactin–lipid II interactions in membranes
Authors: Wen Po-Chao , Vanegas Juan M. , Rempe Susan B. , Tajkhorshid Emad
Published: July 2018

Two binding poses of the teixobactin–lipid II complex were captured with MD simulations at the membrane surface.
Metal–organic framework-based nanofiber filters for effective indoor air quality control
Authors: Bian Ye , Wang Rutao , Wang Shijie , Yao Chenyu , Ren Wei , Chen Chun , Zhang Li
Published: July 2018

MOF-based nanofiber filters via a scalable synthetic strategy serve a dual role in removing both PM2.5 and formaldehyde effectively.
Designing effective Si/Ag interface via controlled chemical etching for photoelectrochemical CO2 reduction
Authors: Hu Yongpan , Chen Fengjiao , Ding Pan , Yang Hui , Chen Junmei , Zha Chenyang , Li Yanguang
Published: July 2018

Controlled chemical etching of Si wafer by Ag+ ions results in the effective Si/Ag interface for photoelectrochemical CO2 reduction to CO.
Tunable CoFe-based active sites on 3D heteroatom doped graphene aerogel electrocatalysts via annealing gas regulation for efficient water splitting
Authors: Zhang Baohua , Wang Haixu , Zuo Zhuang , Wang Huaisheng , Zhang Jintao
Published: July 2018

Tuning CoFe-based active sites on 3D heteroatom doped graphene aerogels facilitates the regulation of the electrocatalytic activity toward the OER and HER, respectively, for efficient water splitting, which is achieved by changing the annealing gas.
Pulsatile release from a flat self-oscillating chitosan macrogel
Authors: Anna Isakova , Katarina Novakovic
Published: July 2018

Pulsatile release of a drug load is reported for the first time from self-oscillating chitosan macrogel, fully concomitant with changes in pH.