bluuebunny/crossref_metadata_2025 huggingface dataset:
Polygenic pleiotropy and potential causal relationships between educational attainment, neurobiological profile, and positive psychotic symptoms
Authors: Lin Yen-Feng , Chen Chia-Yen , Öngür Dost , Betensky Rebecca , Smoller Jordan W. , Blacker Deborah , Hall Mei-Hua
Published: May 2018

Event-related potential (ERP) components have been used to assess cognitive functions in patients with psychotic illness. Evidence suggests that among patients with psychosis there is a distinct heritable neurophysiologic phenotypic subtype captured by impairments across a range of ERP measures. In this study, we investigated the genetic basis of this “globally impaired” ERP cluster and its relationship to psychosis and cognitive abilities. We applied K-means clustering to six ERP measures to re-derive the globally impaired (n = 60) and the non-globally impaired ERP clusters (n = 323) in a sample of cases with schizophrenia (SCZ = 136) or bipolar disorder (BPD = 121) and healthy controls (n = 126). We used genome-wide association study (GWAS) results for SCZ, BPD, college completion, and childhood intelligence as the discovery datasets to derive polygenic risk scores (PRS) in our study sample and tested their associations with globally impaired ERP. We conducted mediation analyses to estimate the proportion of each PRS effect on severity of psychotic symptoms that is mediated through membership in the globally impaired ERP. Individuals with globally impaired ERP had significantly higher PANSS-positive scores (β = 3.95, P = 0.005). The SCZ-PRS was nominally associated with globally impaired ERP (unadjusted P = 0.01; R2 = 3.07%). We also found a significant positive association between the college-PRS and globally impaired ERP (FDR-corrected P = 0.004; R2 = 6.15%). The effect of college-PRS on PANSS positivity was almost entirely (97.1%) mediated through globally impaired ERP. These results suggest that the globally impaired ERP phenotype may represent some aspects of brain physiology on the path between genetic influences on educational attainment and psychotic symptoms.
Activated dendritic cells modulate proliferation and differentiation of human myoblasts
Authors: Ladislau Leandro , Portilho Débora M. , Courau Tristan , Solares-Pérez Alhondra , Negroni Elisa , Lainé Jeanne , Klatzmann David , Bonomo Adriana , Allenbach Yves , Benveniste Olivier , Riederer Ingo , Savino Wilson , Mouly Vincent , Butler-Browne Gillian , Benjamim Claudia F.
Published: May 2018

Idiopathic Inflammatory Myopathies (IIMs) are a heterogeneous group of autoimmune diseases affecting skeletal muscle tissue homeostasis. They are characterized by muscle weakness and inflammatory infiltration with tissue damage. Amongst the cells in the muscle inflammatory infiltration, dendritic cells (DCs) are potent antigen-presenting and key components in autoimmunity exhibiting an increased activation in inflamed tissues. Since, the IIMs are characterized by the focal necrosis/regeneration and muscle atrophy, we hypothesized that DCs may play a role in these processes. Due to the absence of a reliable in vivo model for IIMs, we first performed co-culture experiments with immature DCs (iDC) or LPS-activated DCs (actDC) and proliferating myoblasts or differentiating myotubes. We demonstrated that both iDC or actDCs tightly interact with myoblasts and myotubes, increased myoblast proliferation and migration, but inhibited myotube differentiation. We also observed that actDCs increased HLA-ABC, HLA-DR, VLA-5, and VLA-6 expression and induced cytokine secretion on myoblasts. In an in vivo regeneration model, the co-injection of human myoblasts and DCs enhanced human myoblast migration, whereas the absolute number of human myofibres was unchanged. In conclusion, we suggest that in the early stages of myositis, DCs may play a crucial role in inducing muscle-damage through cell–cell contact and inflammatory cytokine secretion, leading to muscle regeneration impairment.
SIRT1 activation with neuroheal is neuroprotective but SIRT2 inhibition with AK7 is detrimental for disconnected motoneurons
Authors: Romeo-Guitart David , Leiva-Rodríguez Tatiana , Espinosa-Alcantud María , Sima Núria , Vaquero Alejandro , Domínguez- Martín Helena , Ruano Diego , Casas Caty
Published: May 2018

Sirtuin 1 (SIRT1) activity is neuroprotective, and we have recently demonstrated its role in the retrograde degenerative process in motoneurons (MNs) in the spinal cord of rats after peripheral nerve root avulsion (RA) injury. SIRT2 has been suggested to exert effects opposite those of SIRT1; however, its roles in neurodegeneration and neuron response after nerve injury remain unclear. Here we compared the neuroprotective potentials of SIRT1 activation and SIRT2 inhibition in a mouse model of hypoglossal nerve axotomy. This injury induced a reduction of around half MN population within the hypoglossal nucleus by a non-apoptotic neurodegenerative process triggered by endoplasmic reticulum (ER) stress that resulted in activation of the unfolded protein response mediated by IRE1α and XBP1 by 21 days post injury. Both SIRT1 activation with NeuroHeal and SIRT2 inhibition with AK7 protected NSC-34 motor neuron-like cells against ER stress in vitro. In agreement with the in vitro results, NeuroHeal treatment or SIRT1 overexpression was neuroprotective of axotomized hypoglossal MNs in a transgenic mouse model. In contrast, AK7 treatment or SIRT2 genetic depletion in mice inhibited damaged MN survival. To resolve the in vitro/in vivo discrepancies, we used an organotypic spinal cord culture system that preserves glial cells. In this system, AK7 treatment of ER-stressed organotypic cultures was detrimental for MNs and increased microglial nuclear factor-κB and the consequent transcription of cytotoxic pro-inflammatory factors similarly. The results highlight the importance of glial cells in determining the neuroprotective impact of any treatment.
MiR-455-3p inhibits the degenerate process of chondrogenic differentiation through modification of DNA methylation
Authors: Sun Hao , Zhao Xiaoyi , Zhang Chengyun , Zhang Ziji , Lun Jiayong , Liao Weiming , Zhang Zhiqi
Published: May 2018

The aim of this work was to determine whether miR-455-3p regulates DNA methylation during chondrogenic differentiation of hMSCs. The expression of miR-455-3p and de novo methyltransferase DNMT3A was assessed in micromass culture of hBMSCs, which induced chondrogenic differentiation in vitro, and in E16.5 mice in vivo. A luciferase reporter assay was used to confirm whether miR-455-3p directly targets DNMT3A by interaction with the 3′-UTR. Using an Illumina Infinium Methylation EPIC microarray, genome-wide DNA methylation of hBMSCs with or without overexpressed miR-455-3p was examined for 28 days during induced chondrogenic differentiation. Here, we showed that miR-455-3p was more expressed during the middle stage of hBMSC chondrogenic differentiation, and less expressed in the late stage. DNMT3A was less expressed in the middle stage and more expressed in the late stage, and was also more expressed in the palms of miR-455-3p deletion mice compared to those of wild-type mice. The luciferase reporter assay demonstrated that miR-455-3p directly targets DNMT3A 3′-UTR. miR-455-3p overexpression inhibits the degenerate process during chondrogenic differentiation, while deletion of miR-455-3p in mice accelerated cartilage degeneration. Genome-wide DNA methylation analysis showed miR-455-3p overexpression regulates DNA methylation of cartilage-specific genes. GO analysis revealed PI3K-Akt signaling pathway was most hypomethylated. Our data show that miR-455-3p can regulate hMSC chondrogenic differentiation by affecting DNA methylation. Overexpression of miR-455-3p and DNA methylation inhibitors can thus potentially be utilized to optimize chondrogenic differentiation.
Plasma microRNA panel is a novel biomarker for focal segmental glomerulosclerosis and associated with podocyte apoptosis
Authors: Xiao Bin , Wang Li-Na , Li Wei , Gong Li , Yu Ting , Zuo Qian-Fei , Zhao Hong-Wen , Zou Quan-Ming
Published: May 2018

Focal segmental glomerulosclerosis (FSGS) is a frequent glomerular disease, and is the common cause of nephrotic syndrome. However, there is no validated diagnostic blood biomarker for FSGS. Here, we performed a real-time PCR-based high-throughput miRNA profiling to identify the plasma signature for FSGS. We found four miRNAs (miR-17, miR-451, miR-106a, and miR-19b) were significantly downregulated in the plasma of FSGS patients (n = 97) compared with healthy controls (n = 124) in the training, validation, and blinded-test phases. The miRNA panel produced an AUC value of 0.82, and was associated with FSGS severity and histologic classification. A three-miRNA panel, including miR-17, miR-451, and miR-106a was related to FSGS remission. Furthermore, the downregulation of plasma-miRNA signature was not detected in disease controls (n = 119) such as IgA nephropathy (IgAN), mesangial proliferative glomerulonephritis (MSPGN), and membranous nephropathy (MN), and the miRNA panel discriminated between FSGS and disease controls. Pathway analysis showed that the four-miRNA panel may cooperatively regulate the pathways involved in the development of FSGS, such as apoptosis. We identified that phosphatase and tensin homolog (PTEN), Bcl-2-like protein 11 (BCL2L11), and chemokine (C-X-C motif) ligand 14 (CXCL14) were targets of miR-106a in human podocyte. Additionally, miR-106a overexpression suppressed podocyte apoptosis in vitro and the downregulation of four-miRNA panel probably resulted in the enhanced apoptosis in podocyte during FSGS development. Taken together, our data show that the plasma-miRNA panel is a potential independent diagnostic and prognostic factor for FSGS. Above miRNAs are involved in FSGS pathogenesis through regulating podocyte apoptosis.
Stanniocalcin-2 contributes to mesenchymal stromal cells attenuating murine contact hypersensitivity mainly via reducing CD8+ Tc1 cells
Authors: Chen Xiaoyong , Liu Qiuli , Huang Weijun , Cai Chuang , Xia Wenjie , Peng Yanwen , Zheng Shuwei , Li Gang , Xu Yan , Wang Jiancheng , Liu Chang , Zhang Xiaoran , Huang Li , Xiang Andy Peng , Zhang Qi
Published: May 2018

Mesenchymal stromal cells (MSCs) have been demonstrated to ameliorate allergic contact dermatitis (ACD), a typical T-cell-mediated disorder. However, the underlying mechanisms behind the MSC-based treatment for ACD have not yet been fully elucidated. The stanniocalcins (STCs) comprise a family of secreted glycoprotein hormones that act as important anti-inflammatory proteins. Here, we investigated the roles of STCs in MSC-mediated T-cell suppression and their potential role in the MSC-based treatment for ACD. Gene expression profiling revealed that STC2, but not STC1, was highly expressed in MSCs. STC2 knockdown in MSCs significantly impaired their effects in reducing TNF-α- and IFN-γ-producing CD8+T cells. Importantly, silencing the STC2 expression in MSCs abated their therapeutic effect on contact hypersensitivity (CHS) in mice, mainly restoring the generation and infiltration of IFN-γ-producing CD8+T cells (Tc1 cells). Mechanistically, STC2 co-localized with heme oxygenase 1 (HO-1) in MSCs, and contributed to MSC-mediated reduction of CD8+Tc1 cells via regulating HO-1 activity. Together, these findings newly identify STC2 as the first stanniocalcin responsible for mediating the immunomodulatory effects of MSCs on allogeneic T cells and STC2 contribute to MSC-based treatment for ACD mainly via reducing the CD8+Tc1 cells.
Simulated microgravity induces a cellular regression of the mature phenotype in human primary osteoblasts
Authors: Gioia Magda , Michaletti Anna , Scimeca Manuel , Marini Mario , Tarantino Umberto , Zolla Lello , Coletta Massimo
Published: May 2018

Decreased mechanical loading on bones, such as prolonged bed rest and microgravity during space flights, leads to the development of an osteoporotic-like phenotype. Although osteoblast hypo-functionality is reported to be involved in the progression of bone pathological conditions, the cellular mechanisms of this process remain largely unknown. The combined application of mass spectrometry “–omics” and histochemical and ultrastructural approaches have been employed to investigate the effects of the gravitational unloading on human bone-cell biology. Here we show, ex vivo, that simulated microgravity (Sμg) on human primary osteoblasts (hpOB) induces an alteration of pro-osteogenic determinants (i.e., cell morphology and deposit of hydroxyapatite crystals), accompanied by a downregulation of adhesive proteins and bone differentiation markers (e.g., integrin beta-1, protein folding Crystallin Alpha B (CRYα-B), runt-related transcription factor 2 (RUNX-2), bone morphogenic protein-2 (BMP-2), and receptor activator of nuclear factor kappa-B ligand (RANK-L)), indicating an impairment of osteogenesis. Further, we observed for the first time that Sμg can trigger a transition toward a mesenchymal-like phenotype, in which a mature osteoblast displays an hampered vitamin A metabolism, loses adhesive molecules, gains mesenchymal components (e.g., pre-osteoblast state marker CD44), morphological protrusions (filopodium-like), enhances GTPase activities, which in turn allows it to acquire migrating properties. Although this phenotypic conversion is not complete and can be reversible, Sμg environment proves a plasticity potential hidden on Earth. Overall, our results suggest that Sμg can be a powerful physical cue for triggering ex vivo a dedifferentiation impulse on hpOBs, opening a new scenario of possible innovative therapeutical biomechanical strategies for the treatment of osteo-degenerative diseases.
The p53 activator overcomes resistance to ALK inhibitors by regulating p53-target selectivity in ALK-driven neuroblastomas
Authors: Miyazaki Makoto , Otomo Ryo , Matsushima-Hibiya Yuko , Suzuki Hidenobu , Nakajima Ayana , Abe Naomi , Tomiyama Arata , Ichimura Koichi , Matsuda Koichi , Watanabe Toshiki , Ochiya Takahiro , Nakagama Hitoshi , Sakai Ryuichi , Enari Masato
Published: May 2018

Anaplastic lymphoma kinase (ALK) is an oncogenic receptor tyrosine kinase that is activated by gene amplification and mutation in neuroblastomas. ALK inhibitors can delay the progression of ALK-driven cancers, but are of limited use owing to ALK inhibitor resistance. Here, we show that resistance to ALK inhibitor in ALK-driven neuroblastomas can be attenuated by combination treatment with a p53 activator. Either ALK inhibition or p53 activator treatment induced cell cycle arrest, whereas combination treatment induced apoptosis, and prevented tumour relapse both in vitro and in vivo. This shift toward apoptosis, and away from cell-cycle arrest, in the presence of an ALK inhibitor and a p53 activator, is mediated by inhibition of the ALK–AKT–FOXO3a axis leading to a specific upregulation of SOX4. SOX4 cooperates with p53 to upregulate the pro-apoptotic protein PUMA. These data therefore suggest a novel combination therapy strategy for treating ALK-driven neuroblastomas.
Identifying and characterizing SCRaMbLEd synthetic yeast using ReSCuES
Authors: Luo Zhouqing , Wang Lihui , Wang Yun , Zhang Weimin , Guo Yakun , Shen Yue , Jiang Linghuo , Wu Qingyu , Zhang Chong , Cai Yizhi , Dai Junbiao
Published: May 2018

SCRaMbLE is a novel system implemented in the synthetic yeast genome, enabling massive chromosome rearrangements to produce strains with a large genotypic diversity upon induction. Here we describe a reporter of SCRaMbLEd cells using efficient selection, termed ReSCuES, based on a loxP-mediated switch of two auxotrophic markers. We show that all randomly isolated clones contained rearrangements within the synthetic chromosome, demonstrating high efficiency of selection. Using ReSCuES, we illustrate the ability of SCRaMbLE to generate strains with increased tolerance to several stress factors, such as ethanol, heat and acetic acid. Furthermore, by analyzing the tolerant strains, we are able to identify ACE2, a transcription factor required for septum destruction after cytokinesis, as a negative regulator of ethanol tolerance. Collectively, this work not only establishes a generic platform to rapidly identify strains of interest by SCRaMbLE, but also provides methods to dissect the underlying mechanisms of resistance.
Rapid host strain improvement by in vivo rearrangement of a synthetic yeast chromosome
Authors: Blount B. A. , Gowers G-O. F. , Ho J. C. H. , Ledesma-Amaro R. , Jovicevic D. , McKiernan R. M. , Xie Z. X. , Li B. Z. , Yuan Y. J. , Ellis T.
Published: May 2018

Synthetic biology tools, such as modular parts and combinatorial DNA assembly, are routinely used to optimise the productivity of heterologous metabolic pathways for biosynthesis or substrate utilisation, yet it is well established that host strain background is just as important for determining productivity. Here we report that in vivo combinatorial genomic rearrangement of Saccharomyces cerevisiae yeast with a synthetic chromosome V can rapidly generate new, improved host strains with genetic backgrounds favourable to diverse heterologous pathways, including those for violacein and penicillin biosynthesis and for xylose utilisation. We show how the modular rearrangement of synthetic chromosomes by SCRaMbLE can be easily determined using long-read nanopore sequencing and we explore experimental conditions that optimise diversification and screening. This synthetic genome approach to metabolic engineering provides productivity improvements in a fast, simple and accessible way, making it a valuable addition to existing strain improvement techniques.
Thirty loci identified for heart rate response to exercise and recovery implicate autonomic nervous system
Authors: Ramírez Julia , Duijvenboden Stefan van , Ntalla Ioanna , Mifsud Borbala , Warren Helen R , Tzanis Evan , Orini Michele , Tinker Andrew , Lambiase Pier D. , Munroe Patricia B.
Published: May 2018

Impaired capacity to increase heart rate (HR) during exercise (ΔHRex), and a reduced rate of recovery post-exercise (ΔHRrec) are associated with higher cardiovascular mortality rates. Currently, the genetic basis of both phenotypes remains to be elucidated. We conduct genome-wide association studies (GWASs) for ΔHRex and ΔHRrec in ~40,000 individuals, followed by replication in ~27,000 independent samples, all from UK Biobank. Six and seven single-nucleotide polymorphisms for ΔHRex and ΔHRrec, respectively, formally replicate. In a full data set GWAS, eight further loci for ΔHRex and nine for ΔHRrec are genome-wide significant (P ≤ 5 × 10−8). In total, 30 loci are discovered, 8 being common across traits. Processes of neural development and modulation of adrenergic activity by the autonomic nervous system are enriched in these results. Our findings reinforce current understanding of HR response to exercise and recovery and could guide future studies evaluating its contribution to cardiovascular risk prediction.
Molecular solar thermal energy storage in photoswitch oligomers increases energy densities and storage times
Authors: Mansø Mads , Petersen Anne Ugleholdt , Wang Zhihang , Erhart Paul , Nielsen Mogens Brøndsted , Moth-Poulsen Kasper
Published: May 2018

Molecular photoswitches can be used for solar thermal energy storage by photoisomerization into high-energy, meta-stable isomers; we present a molecular design strategy leading to photoswitches with high energy densities and long storage times. High measured energy densities of up to 559 kJ kg−1 (155 Wh kg−1), long storage lifetimes up to 48.5 days, and high quantum yields of conversion of up to 94% per subunit are demonstrated in norbornadiene/quadricyclane (NBD/QC) photo-/thermoswitch couples incorporated into dimeric and trimeric structures. By changing the linker unit between the NBD units, we can at the same time fine-tune light-harvesting and energy densities of the dimers and trimers so that they exceed those of their monomeric analogs. These new oligomers thereby meet several of the criteria to be met for an optimum molecule to ultimately enter actual devices being able to undergo closed cycles of solar light-harvesting, energy storage, and heat release.
Rapid pathway prototyping and engineering using in vitro and in vivo synthetic genome SCRaMbLE-in methods
Authors: Liu Wei , Luo Zhouqing , Wang Yun , Pham Nhan T. , Tuck Laura , Pérez-Pi Irene , Liu Longying , Shen Yue , French Chris , Auer Manfred , Marles-Wright Jon , Dai Junbiao , Cai Yizhi
Published: May 2018

Exogenous pathway optimization and chassis engineering are two crucial methods for heterologous pathway expression. The two methods are normally carried out step-wise and in a trial-and-error manner. Here we report a recombinase-based combinatorial method (termed “SCRaMbLE-in”) to tackle both challenges simultaneously. SCRaMbLE-in includes an in vitro recombinase toolkit to rapidly prototype and diversify gene expression at the pathway level and an in vivo genome reshuffling system to integrate assembled pathways into the synthetic yeast genome while combinatorially causing massive genome rearrangements in the host chassis. A set of loxP mutant pairs was identified to maximize the efficiency of the in vitro diversification. Exemplar pathways of β-carotene and violacein were successfully assembled, diversified, and integrated using this SCRaMbLE-in method. High-throughput sequencing was performed on selected engineered strains to reveal the resulting genotype-to-phenotype relationships. The SCRaMbLE-in method proves to be a rapid, efficient, and universal method to fast track the cycle of engineering biology.
Asynchronous suppression of visual cortex during absence seizures in stargazer mice
Authors: Meyer Jochen , Maheshwari Atul , Noebels Jeffrey , Smirnakis Stelios
Published: May 2018

Absence epilepsy is a common childhood disorder featuring frequent cortical spike-wave seizures with a loss of awareness and behavior. Using the calcium indicator GCaMP6 with in vivo 2-photon cellular microscopy and simultaneous electrocorticography, we examined the collective activity profiles of individual neurons and surrounding neuropil across all layers in V1 during spike-wave seizure activity over prolonged periods in stargazer mice. We show that most (~80%) neurons in all cortical layers reduce their activity during seizures, whereas a smaller pool activates or remains neutral. Unexpectedly, ictal participation of identified single-unit activity is not fixed, but fluctuates on a flexible time scale from seizure to seizure. Pairwise correlation analysis of calcium activity reveals a surprising lack of synchrony among neurons and neuropil patches in all layers during seizures. Our results demonstrate asynchronous suppression of visual cortex during absence seizures, with potential implications for understanding cortical network function during EEG states of reduced awareness.
Effect of ionic composition on thermal properties of energetic ionic liquids
Authors: Park Chihyun , Han Minsu , Kim Jinbo , Lee Woojae , Kim Eunkyoung
Published: May 2018

A model to predict the effect of ionic composition on the thermal properties of energetic ionic liquids was developed by quantitative structure-property relationship modeling, which predicted the detonation velocity, pressure, and melting temperature of energetic ionic liquids. A hybrid approach was used to determine the optimal subset of descriptors by combining regression with the genetic algorithm as an optimization method. The model showed the high accuracy, reaching a correlation factor of R2 as 0.71, 0.73 and 0.68 for the correlation between the calculated detonation velocity, pressure and melting temperature against reported values. It was validated extensively and compared to the Kamlet–Jacobs equation. The effect of ion composition on the thermal properties of energetic ionic liquids could be quantitatively analyzed through the developed model, to give an insight for the design of new energetic ionic liquids.
Author Correction: Abnormal Paraventricular Nucleus of Hypothalamus and Growth Retardation Associated with Loss of Nuclear Receptor Gene COUP-TFII
Authors: Feng Su , Xing Can , Shen Tingyu , Qiao Yunbo , Wang Ran , Chen Jun , Liao Jiaoyang , Lu Zhuo , Yang Xiong , Abd-Allah Saber Mohamed , Li Jinsong , Jing Naihe , Tang Ke
Published: May 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Slow touch targeting CT-fibres does not increase prosocial behaviour in economic laboratory tasks
Authors: Rosenberger Lisa Anna , Ree Anbjørn , Eisenegger Christoph , Sailer Uta
Published: May 2018

Field studies have demonstrated that humans become more generous, helpful and compliant after having been touched by another person. Here, we explored whether these effects are larger for touch activating the C-tactile (CT) fibres, as it is ascribed a particular role in establishing and maintaining bonds and affiliative interactions. The role of CT-targeted and non-targeted touch on prosocial behaviour was investigated in three different experiments using a trust game and a task measuring individual differences in social value orientations (the SVO task). Whereas participants in general acted prosocially, there was no influence of CT-targeted touch on prosocial behaviour, both in comparison to non-CT-targeted control touch and visual (non-tactile) stimulation. The null findings were further corroborated by Bayesian statistics. Thus, under the controlled laboratory conditions employed, CT-targeted touch did not play a particular role in prosocial behaviour. This indicates that touch does not increase prosocial behaviour in the absence of meaningful social and psychological connotations. Any touch related effects on prosocial behaviour likely depends on the ecological validity of the situation.
Effectiveness of in-Line Filters to Completely Remove Particulate Contamination During a Pediatric Multidrug Infusion Protocol
Authors: Perez Maxime , Décaudin Bertrand , Abou Chahla Wadih , Nelken Brigitte , Storme Laurent , Masse Morgane , Barthélémy Christine , Lebuffe Gilles , Odou Pascal
Published: May 2018

The large number of drugs administered simultaneously to neonates and children in hospital results in the formation of particles that are potentially infused. We have investigated the ability of IV in-line filters to eliminate particulate matter from multidrug infusion lines and so prevent contamination. The impact on particle occurrence of the internal volume of the IV line below the in-line filter was then evaluated. The multidrug therapy given to children was reproduced with and without in-line filtration. Three combinations with a filter were tested to vary the internal volume (V) between the filter and the catheter egress. The catheter was then connected to a dynamic particle count to evaluate the particulate matter potentially administered to children during infusion. The introduction of in-line filters led to a significant reduction in overall particulate matter, from 416,974 [208,479–880,229] to 7,551 [1,985–11,287] particles (p < 0.001). Larger particles of ≥10 and 25 µm were also significantly reduced. Adding an extension set to the egress of the in-line filter (V = 1.7 mL) caused a significant increase in particulate contamination for both. This study showed that in-line filtration is an effective tool in preventing particle administration to patients. Their position in the infusion in-line is therefore important because of its impact on internal volume and drug particle formation.
Cattle with a precise, zygote-mediated deletion safely eliminate the major milk allergen beta-lactoglobulin
Authors: Wei Jingwei , Wagner Stefan , Maclean Paul , Brophy Brigid , Cole Sally , Smolenski Grant , Carlson Dan F. , Fahrenkrug Scott C. , Wells David N. , Laible Götz
Published: May 2018

We applied precise  zygote-mediated genome editing to eliminate beta-lactoglobulin (BLG), a major allergen in cows’ milk. To efficiently generate LGB knockout cows, biopsied embryos were screened to transfer only appropriately modified embryos. Transfer of 13 pre-selected embryos into surrogate cows resulted in the birth of three calves, one dying shortly after birth. Deep sequencing results confirmed conversion of the genotype from wild type to the edited nine bp deletion by more than 97% in the two male calves. The third calf, a healthy female, had in addition to the expected nine bp deletion (81%), alleles with an in frame 21 bp deletion (<17%) at the target site. While her milk was free of any mature BLG, we detected low levels of a BLG variant derived from the minor deletion allele. This confirmed that the nine bp deletion genotype completely knocks out production of BLG. In addition, we showed that the LGB knockout animals are free of any TALEN-mediated off-target mutations or vector integration events using an unbiased whole genome analysis. Our study demonstrates the feasibility of generating precisely biallelically edited cattle by zygote-mediated editing for the safe production of hypoallergenic milk.
Short-term temporal memory in idiopathic and Parkin-associated Parkinson’s disease
Authors: Degos Bertrand , Ameqrane Ilhame , Rivaud-Péchoux Sophie , Pouget Pierre , Missal Marcus
Published: May 2018

In a rapidly changing environment, we often know when to do something before we have to do it. This preparation in the temporal domain is based on a ‘perception’ of elapsed time and short-term memory of previous stimulation in a similar context. These functions could be perturbed in Parkinson’s disease. Therefore, we investigated their role in eye movement preparation in sporadic Parkinson’s disease and in a very infrequent variant affecting the Parkin gene. We used a simple oculomotor task where subjects had to orient to a visual target and movement latency was measured. We found that in spite of an increased average reaction time, the influence of elapsed time on movement preparation was similar in controls and the two groups of PD patients. However, short-term temporal memory of previous stimulation was severely affected in sporadic PD patients either ON or OFF dopaminergic therapy. We conclude that the two different contributions to temporal preparation could be dissociated. Moreover, a short-term temporal memory deficit might underlie temporal cognition deficits previously observed in PD.
Yttrium (III) Recovery with D2EHPA in Pseudo-Emulsion Hollow Fiber Strip Dispersion System
Authors: Pirom Teerapon , Arponwichanop Amornchai , Pancharoen Ura , Yonezawa Tetsu , Kheawhom Soorathep
Published: May 2018

Yttrium (Y) is an essential lanthanide rare earth element and can be effectively extracted and purified using a hollow fiber supported liquid membrane (HFSLM) system. However, the stability of HFSLM system is a significant challenge. Pseudoemulsion-hollow fiber strip dispersion (PEHFSD) system, providing excellent stability, is attracting research attention. In this work, the recovery of Y(III) by PEHFSD system using di(2-ethylhexyl)phosphoric acid (D2EHPA) as a carrier was investigated. The effects of several operating parameters, including the initial concentration of Y(III) in the feed phase, the flow rate of feed, the stirring speed and the volumetric ratio of feed to strip on Y(III) separation were studied. The Y(III) transport was analyzed on the concentration ratio of Y(III) ions, percent extraction, percent stripping and overall mass transfer coefficient (K
p
). The PEHFSD system outperformed HFSLM system regarding separation performance and stability. K
p
of HFSLM system decreased after the second run, but K
p
of PEHFSD system remained constant even at the fifth run. The dispersed droplets in the strip dispersion phase in the PEHFSD system enhanced separation performance and stability of the membrane module.
Common drivers of seasonal movements on the migration – residency behavior continuum in a large herbivore
Authors: Martin Jodie , Tolon Vincent , Morellet Nicolas , Santin-Janin Hugues , Licoppe Alain , Fischer Claude , Bombois Jérôme , Patthey Patrick , Pesenti Elias , Chenesseau Delphine , Saïd Sonia
Published: May 2018

This study aimed to (1) identify the scale of environmental drivers of seasonal movements on the migration – residency behavior continuum in a large herbivore species and to (2) test the hypothesis that the same environmental drivers and spatio-temporal scaling should influence spatial processes in both migrants (long distance migration) and residents (short distance range shifts). We performed a comparative analysis of the influence of plant phenology and snow cover duration on seasonal movements of five partially migrating red deer populations with contrasting environmental conditions, at the seasonal range scale and at the study area scale. The five populations presented varying proportions of migrants, large gradients of migration distances and seasonal range shifts. The probability for a red deer to migrate was strongly influenced by large-scale environmental conditions, consistent with the resource heterogeneity hypothesis (high spatio-temporal scaling favors migration). Distances moved by both migrants and residents were strongly related to large-scale environmental conditions as well. We showed that similar proximal causes influenced these seasonal movements, reinforcing the idea of a continuum from migration to residency in response to seasonal environmental changes. Together, our findings suggest that global warming, by homogenizing large-scale environmental conditions, may thus decrease migratory tactics.
Possible role of the Nipah virus V protein in the regulation of the interferon beta induction by interacting with UBX domain-containing protein1
Authors: Uchida Shotaro , Horie Ryo , Sato Hiroki , Kai Chieko , Yoneda Misako
Published: May 2018

Nipah virus (NiV) is a highly pathogenic paramyxovirus that causes lethal encephalitis in humans. We previously reported that the V protein, one of the three accessory proteins encoded by the P gene, is one of the key determinants of the pathogenesis of NiV in a hamster infection model. Satterfield B.A. et al. have also revealed that V protein is required for the pathogenicity of henipavirus in a ferret infection model. However, the complete functions of NiV V have not been clarified. In this study, we identified UBX domain-containing protein 1 (UBXN1), a negative regulator of RIG-I-like receptor signaling, as a host protein that interacts with NiV V. NiV V interacted with the UBX domain of UBXN1 via its proximal zinc-finger motif in the C-terminal domain. NiV V increased the level of UBXN1 protein by suppressing its proteolysis. Furthermore, NiV V suppressed RIG-I and MDA5-dependent interferon signaling by stabilizing UBXN1 and increasing the interaction between MAVS and UBXN1 in addition to directly interrupting the activation of MDA5. Our results suggest a novel molecular mechanism by which the induction of interferon is potentially suppressed by NiV V protein via UBXN1.
Unsaturation of vapour pressure inside leaves of two conifer species
Authors: Cernusak Lucas A. , Ubierna Nerea , Jenkins Michael W. , Garrity Steven R. , Rahn Thom , Powers Heath H. , Hanson David T. , Sevanto Sanna , Wong Suan Chin , McDowell Nate G. , Farquhar Graham D.
Published: May 2018

Stomatal conductance (gs) impacts both photosynthesis and transpiration, and is therefore fundamental to the global carbon and water cycles, food production, and ecosystem services. Mathematical models provide the primary means of analysing this important leaf gas exchange parameter. A nearly universal assumption in such models is that the vapour pressure inside leaves (ei) remains saturated under all conditions. The validity of this assumption has not been well tested, because so far ei cannot be measured directly. Here, we test this assumption using a novel technique, based on coupled measurements of leaf gas exchange and the stable isotope compositions of CO2 and water vapour passing over the leaf. We applied this technique to mature individuals of two semiarid conifer species. In both species, ei routinely dropped below saturation when leaves were exposed to moderate to high air vapour pressure deficits. Typical values of relative humidity in the intercellular air spaces were as low 0.9 in Juniperus monosperma and 0.8 in Pinus edulis. These departures of ei from saturation caused significant biases in calculations of gs and the intercellular CO2 concentration. Our results refute the longstanding assumption of saturated vapour pressure in plant leaves under all conditions.
Optimal Design of Miniaturized Reflecting Metasurfaces for Ultra-Wideband and Angularly Stable Polarization Conversion
Authors: Borgese Michele , Costa Filippo , Genovesi Simone , Monorchio Agostino , Manara Giuliano
Published: May 2018

An ultra-wideband linear polarization converter based on a reflecting metasurface is presented. The polarizer is composed by a periodic arrangement of miniaturized metallic elements printed on a grounded dielectric substrate. In order to achieve broadband polarization converting properties, the metasurface is optimized by employing a genetic algorithm (GA) which imposes the minimization of the amplitude of the co-polar reflection coefficient over a wide frequency band. The enhanced angular stability of the polarization converter is due to the miniaturized unit cell which is obtained by imposing the maximum periodicity of the metasurface in the GA optimization process. The pixelated polarization converter obtained by the GA exhibits a relative bandwidth of 102% working from 8.12 GHz to 25.16 GHz. The analysis of the surface current distribution of the metasurface led to a methodology for refining the optimized GA solution based on the sequential removal of pixels of the unit cell on which surface currents are not excited. The relative bandwidth of the refined polarizer is extended up to 117.8% with a unit cell periodicity of 0.46 mm, corresponding to λ/20 at the maximum operating frequency. The performance of the proposed ultra-wideband polarization metasurface has been confirmed through full-wave simulations and measurements.
Antiretroviral Drugs Alter the Content of Extracellular Vesicles from HIV-1-Infected Cells
Authors: DeMarino Catherine , Pleet Michelle L. , Cowen Maria , Barclay Robert A. , Akpamagbo Yao , Erickson James , Ndembi Nicaise , Charurat Manhattan , Jumare Jibreel , Bwala Sunday , Alabi Peter , Hogan Max , Gupta Archana , Noren Hooten Nicole , Evans Michele K. , Lepene Benjamin , Zhou Weidong , Caputi Massimo , Romerio Fabio , Royal Walter , El-Hage Nazira , Liotta Lance A. , Kashanchi Fatah
Published: May 2018

To date, the most effective treatment of HIV-1 is a combination antiretroviral therapy (cART), which reduces viral replication and reverses pathology. We investigated the effect of cART (RT and protease inhibitors) on the content of extracellular vesicles (EVs) released from HIV-1-infected cells. We have previously shown that EVs contain non-coding HIV-1 RNA, which can elicit responses in recipient cells. In this manuscript, we show that TAR RNA levels demonstrate little change with the addition of cART treatment in cell lines, primary macrophages, and patient biofluids. We determined possible mechanisms involved in the selective packaging of HIV-1 RNA into EVs, specifically an increase in EV-associated hnRNP A2/B1. More recent experiments have shown that several other FDA-approved drugs have the ability to alter the content of exosomes released from HIV-1-infected cells. These findings on cART-altered EV content can also be applied to general viral inhibitors (interferons) which are used to treat other chronic infections. Additionally, we describe unique mechanisms of ESCRT pathway manipulation by antivirals, specifically the targeting of VPS4. Collectively, these data imply that, despite antiretroviral therapy, EVs containing viral products are continually released and may cause neurocognitive and immunological dysfunction.
In Utero and Postnatal Exposure to High Fat, High Sucrose Diet Suppressed Testis Apoptosis and Reduced Sperm Count
Authors: Mao Jiude , Pennington Kathleen A. , Talton Omonseigho O. , Schulz Laura C. , Sutovsky Miriam , Lin Yan , Sutovsky Peter
Published: May 2018

Obesity affects male fertility and maternal diabetes affects the offspring sperm epigenome. However, the effects of in utero exposure to maternal glucose intolerance in combination with postnatal high fat, high sucrose (HFHS) diet consumption on offspring spermatogenesis is not clear. The present study was designed to test these effects. One week before and during pregnancy, dams were fed either control or HFHS diet to induce gestational glucose intolerance, and returned to standard diet during lactation. Male offspring from each maternal group were split into control and HFHS-fed groups for eight weeks prior to sacrifice at 11, 19 or 31 weeks of age, and reproductive tissues were harvested for analysis of testicular germ cell apoptosis and sperm output. Postnatal HFHS diet suppressed spermatogonia apoptosis in all age groups and maternal HFHS diet reduced testosterone levels at 11 weeks. At 31 weeks of age, the postnatal HFHS diet increased body weight, and reduced epididymis weight and sperm count. The combination of in utero and postnatal exposure impacted sperm counts most significantly. In summary, HFHS diet during pregnancy puts male offspring at greater risk of infertility, particularly when combined with postnatal high fat diet feeding.
Electrically and Thermally Conductive Carbon Fibre Fabric Reinforced Polymer Composites Based on Nanocarbons and an In-situ Polymerizable Cyclic Oligoester
Authors: Jang Ji-un , Park Hyeong Cheol , Lee Hun Su , Khil Myung-Seob , Kim Seong Yun
Published: May 2018

There is growing interest in carbon fibre fabric reinforced polymer (CFRP) composites based on a thermoplastic matrix, which is easy to rapidly produce, repair or recycle. To expand the applications of thermoplastic CFRP composites, we propose a process for fabricating conductive CFRP composites with improved electrical and thermal conductivities using an in-situ polymerizable and thermoplastic cyclic butylene terephthalate oligomer matrix, which can induce good impregnation of carbon fibres and a high dispersion of nanocarbon fillers. Under optimal processing conditions, the surface resistivity below the order of 10+10 Ω/sq, which can enable electrostatic powder painting application for automotive outer panels, can be induced with a low nanofiller content of 1 wt%. Furthermore, CFRP composites containing 20 wt% graphene nanoplatelets (GNPs) were found to exhibit an excellent thermal conductivity of 13.7 W/m·K. Incorporating multi-walled carbon nanotubes into CFRP composites is more advantageous for improving electrical conductivity, whereas incorporating GNPs is more beneficial for enhancing thermal conductivity. It is possible to fabricate the developed thermoplastic CFRP composites within 2 min. The proposed composites have sufficient potential for use in automotive outer panels, engine blocks and other mechanical components that require conductive characteristics.
Cu/Cu2O nanocomposite films as a p-type modified layer for efficient perovskite solar cells
Authors: Chen You-Jyun , Li Ming-Hsien , Huang Jung-Chun-Andrew , Chen Peter
Published: May 2018

Cu/Cu2O films grown by ion beam sputtering were used as p-type modified layers to improve the efficiency and stability of perovskite solar cells (PSCs) with an n-i-p heterojunction structure. The ratio of Cu to Cu2O in the films can be tuned by the oxygen flow ratio (O2/(O2 + Ar)) during the sputtering of copper. Auger electron spectroscopy was performed to determine the elemental composition and chemical state of Cu in the films. Ultraviolet photoelectron spectroscopy and photoluminescence spectroscopy revealed that the valence band maximum of the p-type Cu/Cu2O matches well with the perovskite. The Cu/Cu2O film not only acts as a p-type modified layer but also plays the role of an electron blocking buffer layer. By introducing the p-type Cu/Cu2O films between the low-mobility hole transport material, spiro-OMeTAD, and the Ag electrode in the PSCs, the device durability and power conversion efficiency (PCE) were effectively improved as compared to the reference devices without the Cu/Cu2O interlayer. The enhanced PCE is mainly attributed to the high hole mobility of the p-type Cu/Cu2O film. Additionally, the Cu/Cu2O film serves as a protective layer against the penetration of humidity and Ag into the perovskite active layer.
Characterization of antennal chemosensilla and associated odorant binding as well as chemosensory proteins in the parasitoid wasp Microplitis mediator (Hymenoptera: Braconidae)
Authors: Wang Shan-Ning , Shan Shuang , Liu Jing-Tao , Li Rui-Jun , Lu Zi-Yun , Dhiloo Khalid Hussain , Khashaveh Adel , Zhang Yong-Jun
Published: May 2018

Odorant binding proteins (OBPs) and chemosensory proteins (CSPs) expressed in antennal chemosensilla are believed to be important in insect chemoreception. In the current study, we fully described the morphological characteristics of the antennal sensilla in parasitoid wasp Microplitis mediator and analyzed the expression patterns of OBPs and CSPs within the antennae. In M. mediator, eight types of sensilla were observed on the antennae. Sensilla basiconica type 2 and s. placodea with wall pores may be involved in olfactory perception, whereas s. basiconica type 1 and type 3 with tip pores may play gustatory functions. Among the 18 OBPs and 3 CSPs in M. mediator, 10 OBPs and 2 CSPs were exclusively or primarily expressed in the antennae. In situ hybridization experiments indicated that the 12 antennae-enriched OBPs and CSPs were mapped to five morphological classes of antennal sensilla, including s. basiconica (type 1–3), s. placodea and s. coeloconica. Within the antennae, most of OBP and CSP genes were expressed only in one type of sensilla indicating their differentiated roles in detection of special type of chemical molecules. Our data will lay a foundation to further study the physiological roles of OBPs and CSPs in antennae of parasitoid wasps.
Touchscreen typing-pattern analysis for detecting fine motor skills decline in early-stage Parkinson’s disease
Authors: Iakovakis Dimitrios , Hadjidimitriou Stelios , Charisis Vasileios , Bostantzopoulou Sevasti , Katsarou Zoe , Hadjileontiadis Leontios J.
Published: May 2018

Parkinson’s disease (PD) is a degenerative movement disorder causing progressive disability that severely affects patients’ quality of life. While early treatment can produce significant benefits for patients, the mildness of many early signs combined with the lack of accessible high-frequency monitoring tools may delay clinical diagnosis. To meet this need, user interaction data from consumer technologies have recently been exploited towards unsupervised screening for PD symptoms in daily life. Similarly, this work proposes a method for detecting fine motor skills decline in early PD patients via analysis of patterns emerging from finger interaction with touchscreen smartphones during natural typing. Our approach relies on low-/higher-order statistical features of keystrokes timing and pressure variables, computed from short typing sessions. Features are fed into a two-stage multi-model classification pipeline that reaches a decision on the subject’s status (PD patient/control) by gradually fusing prediction probabilities obtained for individual typing sessions and keystroke variables. This method achieved an AUC = 0.92 and 0.82/0.81 sensitivity/specificity (matched groups of 18 early PD patients/15 controls) with discriminant features plausibly correlating with clinical scores of relevant PD motor symptoms. These findings suggest an improvement over similar approaches, thereby constituting a further step towards unobtrusive early PD detection from routine activities.