bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of the QBO on Prediction and Predictability of the MJO Convection
Authors: Wang Shuguang , Tippett Michael K. , Sobel Adam H. , Martin Zane K. , Vitart Frederic
Published: November 2019

The impact of the quasi‐biennial oscillation (QBO) on the prediction of tropical intraseasonal convection, including the Madden Julian Oscillation (MJO) and Boreal Summer Intraseasonal Oscillation (BSISO), is assessed in the WMO Subseasonal to Seasonal (S2S) forecast database using the real‐time OLR based MJO (ROMI) index. It is shown that the ROMI prediction skill for the boreal winter MJO, measured by the maximum time at which the anomaly correlation coefficient exceeds 0.6, is higher by 5 to 10 days in the QBO easterly phase than its westerly phase. This difference occurs even in models with low tops and poorly resolved stratospheres. MJO predictability, as measured by signal to noise ratio in the S2S ensemble, also shows a similar difference between the two QBO phases, and results from a simple linear regression model show consistent behavior as well. Analysis of the ROMI index derived from observations indicates that the MJO is more coherent and stronger in the QBO easterly phase than in the westerly phase. These results suggest that the skill dependence on QBO phase results from the initial state of the MJO, the regularity of its propagation in the verifying observations, or most likely a combination of the two, but not on an actual stratospheric influence on the MJO within the model simulations. In contrast to the robust QBO‐MJO connection in boreal winter, the BSISO prediction skill exhibited by the S2S models in boreal summer is greater in the QBO westerly phase than in the easterly phase during the 1999 to 2010 period. This is consistent with the observation that BSISO OLR anomalies are stronger in the QBO westerly phase during that period. However, this relationship between the QBO and BSISO in boreal summer changes in recent decades: BSISO is weaker in QBO westerly than easterly during 1979–2000. Correspondingly, the QBO impact on BSISO prediction in boreal summer also reverses in that period as well in a statistical model, whereas this statistical model shows a consistent QBO impact on MJO prediction in boreal winter over the past four decades.
Aerosol Properties Over Tibetan Plateau From a Decade of AERONET Measurements: Baseline, Types, and Influencing Factors
Authors: Pokharel Manisha , Guang Jie , Liu Bin , Kang Shichang , Ma Yaoming , Holben Brent N. , Xia Xiang'ao , Xin Jinyuan , Ram Kirpa , Rupakheti Dipesh , Wan Xin , Wu Guangming , Bhattarai Hemraj , Zhao Chuanfeng , Cong Zhiyuan
Published: November 2019

In this study, a decade long measurement of aerosol optical properties at two AERONET stations (Nam Co during 2006–2016 and QOMS during 2009–2017) in the Tibetan Plateau (TP), a region sensitive to climate change and human perturbation, is presented. The baseline value of aerosol optical depth (AOD) was 0.029 and 0.027 at Nam Co and QOMS, respectively, which are comparable to or even lower than those at some Arctic and remote ocean locations. The seasonality of AOD values were the order of spring > summer > winter > autumn. Based on AOD and Ångström exponent (α), major aerosol types over the TP were further identified as continental background, biomass burning, and dust. Although continental background aerosol was the main feature in remote areas of TP, biomass burning plumes frequently occurred, especially during spring (March–April). In one of such biomass burning event in April 2014, MODIS observations demonstrated that intensive open fires occurred in South Asia, covering the foothills of Himalayas and Indo‐Gangetic Plain. The air mass back trajectories and CALIOP observations further revealed that biomass burning plume could be uplifted to higher altitudes and reach the Himalayas. Moreover, an occasional dust event detected in April 2008 over the TP demonstrated that the dust from Taklamakan Desert may impact the main body of TP episodically, although the local dust from the inside of TP cannot be excluded and warrants further study.
3D cellular-resolution imaging in arteries using few-mode interferometry
Authors: Yin Biwei , Piao Zhonglie , Nishimiya Kensuke , Hyun Chulho , Gardecki Joseph A. , Mauskapf Adam , Jaffer Farouc A. , Tearney Guillermo J.
Published: November 2019

Cross-sectional visualisation of the cellular and subcellular structures of human atherosclerosis in vivo is significant, as this disease is fundamentally caused by abnormal processes that occur at this scale in a depth-dependent manner. However, due to the inherent resolution-depth of focus tradeoff of conventional focusing optics, today’s highest-resolution intravascular imaging technique, namely, optical coherence tomography (OCT), is unable to provide cross-sectional images at this resolution through a coronary catheter. Here, we introduce an intravascular imaging system and catheter based on few-mode interferometry, which overcomes the depth of focus limitation of conventional high-numerical-aperture objectives and enables three-dimensional cellular-resolution intravascular imaging in vivo by a submillimetre diameter, flexible catheter. Images of diseased cadaver human coronary arteries and living rabbit arteries were acquired with this device, showing clearly resolved cellular and subcellular structures within the artery wall, such as individual crystals, smooth muscle cells, and inflammatory cells. The capability of this technology to enable cellular-resolution, cross-sectional intravascular imaging will make it possible to study and diagnose human coronary disease with much greater precision in the future.
Three genetic–environmental networks for human personality
Authors: Zwir Igor , Del-Val Coral , Arnedo Javier , Pulkki-Råback Laura , Konte Bettina , Yang Sarah S. , Romero-Zaliz Rocio , Hintsanen Mirka , Cloninger Kevin M. , Garcia Danilo , Svrakic Dragan M. , Lester Nigel , Rozsa Sandor , Mesa Alberto , Lyytikäinen Leo-Pekka , Giegling Ina , Kähönen Mika , Martinez Maribel , Seppälä Ilkka , Raitoharju Emma , de Erausquin Gabriel A. , Mamah Daniel , Raitakari Olli , Rujescu Dan , Postolache Teodor T. , Gu C. Charles , Sung Joohon , Lehtimäki Terho , Keltikangas-Järvinen Liisa , Cloninger C. Robert
Published: November 2019

Phylogenetic, developmental, and brain-imaging studies suggest that human personality is the integrated expression of three major systems of learning and memory that regulate (1) associative conditioning, (2) intentionality, and (3) self-awareness. We have uncovered largely disjoint sets of genes regulating these dissociable learning processes in different clusters of people with (1) unregulated temperament profiles (i.e., associatively conditioned habits and emotional reactivity), (2) organized character profiles (i.e., intentional self-control of emotional conflicts and goals), and (3) creative character profiles (i.e., self-aware appraisal of values and theories), respectively. However, little is known about how these temperament and character components of personality are jointly organized and develop in an integrated manner. In three large independent genome-wide association studies from Finland, Germany, and Korea, we used a data-driven machine learning method to uncover joint phenotypic networks of temperament and character and also the genetic networks with which they are associated. We found three clusters of similar numbers of people with distinct combinations of temperament and character profiles. Their associated genetic and environmental networks were largely disjoint, and differentially related to distinct forms of learning and memory. Of the 972 genes that mapped to the three phenotypic networks, 72% were unique to a single network. The findings in the Finnish discovery sample were blindly and independently replicated in samples of Germans and Koreans. We conclude that temperament and character are integrated within three disjoint networks that regulate healthy longevity and dissociable systems of learning and memory by nearly disjoint sets of genetic and environmental influences.
Air mass source determines airborne microbial diversity at the ocean–atmosphere interface of the Great Barrier Reef marine ecosystem
Authors: Archer Stephen D J , Lee Kevin C , Caruso Tancredi , King-Miaow Katie , Harvey Mike , Huang Danwei , Wainwright Benjamin J , Pointing Stephen B
Published: November 2019

The atmosphere is the least understood biome on Earth despite its critical role as a microbial transport medium. The influence of surface cover on composition of airborne microbial communities above marine systems is unclear. Here we report evidence for a dynamic microbial presence at the ocean–atmosphere interface of a major marine ecosystem, the Great Barrier Reef, and identify that recent air mass trajectory over an oceanic or continental surface associated with observed shifts in airborne bacterial and fungal diversity. Relative abundance of shared taxa between air and coral microbiomes varied between 2.2 and 8.8% and included those identified as part of the core coral microbiome. We propose that this variable source of atmospheric inputs may in part contribute to the diverse and transient nature of the coral microbiome.
Evidence that genes involved in hedgehog signaling are associated with both bipolar disorder and high BMI
Authors: Pisanu Claudia , Williams Michael J. , Ciuculete Diana M. , Olivo Gaia , Del Zompo Maria , Squassina Alessio , Schiöth Helgi B.
Published: November 2019

Patients with bipolar disorder (BD) show higher frequency of obesity and type 2 diabetes (T2D), but the underlying genetic determinants and molecular pathways are not well studied. Using large publicly available datasets, we (1) conducted a gene-based analysis using MAGMA to identify genes associated with BD and body mass index (BMI) or T2D and investigated their functional enrichment; and (2) performed two meta-analyses between BD and BMI, as well as BD and T2D using Metasoft. Target druggability was assessed using the Drug Gene Interaction Database (DGIdb). We identified 518 and 390 genes significantly associated with BD and BMI or BD and T2D, respectively. A total of 52 and 12 genes, respectively, were significant after multiple testing correction. Pathway analyses conducted on nominally significant targets showed that genes associated with BD and BMI were enriched for the Neuronal cell body Gene Ontology (GO) term (p = 1.0E−04; false discovery rate (FDR) = 0.025) and different pathways, including the Signaling by Hedgehog pathway (p = 4.8E−05, FDR = 0.02), while genes associated with BD and T2D showed no specific enrichment. The meta-analysis between BD and BMI identified 64 relevant single nucleotide polymorphisms (SNPs). While the majority of these were located in intergenic regions or in a locus on chromosome 16 near and in theNPIPL1andSH2B1genes (best SNP: rs4788101,p = 2.1E−24), five were located in theETV5gene (best SNP: rs1516725,p = 1E−24), which was previously associated with both BD and obesity, and one in theRPGRIP1Lgene (rs1477199,p = 5.7E−09), which was also included in the Signaling by Hedgehog pathway. The meta-analysis between BD and T2D identified six significant SNPs, three of which were located inALAS1(best SNP: rs352165,p = 3.4E−08). Thirteen SNPs associated with BD and BMI, and one with BD and T2D, were located in genes which are part of the druggable genome. Our results support the hypothesis of shared genetic determinants between BD and BMI and point to genes involved in Hedgehog signaling as promising targets.
Correction: Benchmarking of survival outcomes following haematopoietic stem cell transplantation: A review of existing processes and the introduction of an international system from the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE)
Authors: Snowden John A. , Saccardi Riccardo , Orchard Kim , Ljungman Per , Duarte Rafael F. , Labopin Myriam , McGrath Eoin , Brook Nigel , de Elvira Carmen Ruiz , Gordon Debra , Poirel Hélène A. , Ayuk Francis , Beguin Yves , Bonifazi Francesca , Gratwohl Alois , Milpied Noel , Moore John , Passweg Jakob , Rizzo J. Douglas , Spellman Stephen R. , Sierra Jorge , Solano Carlos , Sanchez-Guijo Fermin , Worel Nina , Gusi Andreu , Adams Gillian , Balan Theodor , Baldomero Helen , Macq Gilles , Marry Evelyne , Mesnil Florence , Oldani Elena , Pearce Rachel , Perry Julia , Raus Nicole , Schanz Urs , Tran Steven , Wilcox Leonie , Basak Grzegorz W. , Chabannon Christian , Corbacioglu Selim , Dolstra Harry , Kuball Jürgen , Mohty Mohamad , Lankester Arjan , Montoto Sylvia , Nagler Arnon , Styczynski Jan , Yakoub-Agha Ibrahim , de Latour Regis Peffault , Kroeger Nicolaus , Brand Ronald , de Wreede Liesbeth C. , van Zwet Erik , Putter Hein
Published: November 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Study of the antitumour effects and the modulation of immune response by histamine in breast cancer
Authors: Nicoud Melisa B. , Sterle Helena A. , Massari Noelia A. , Táquez Delgado Mónica A. , Formoso Karina , Herrero Ducloux María V. , Martinel Lamas Diego , Cremaschi Graciela A. , Medina Vanina A.
Published: November 2019

Background

The aim of this work was to improve the knowledge of the role of histamine in breast cancer by assessing the therapeutic efficacy of histamine and histamine H4 receptor (H4R) ligands in a triple-negative breast cancer (TNBC) model developed in immunocompetent hosts. By using publicly available genomic data, we further investigated whether histidine decarboxylase (HDC) could be a potential biomarker.

Methods

Tumours of 4T1 TNBC cells were orthotopically established in BALB/c mice. Treatments employed (mg kg−1): histamine (1 and 5), JNJ28610244 (H4R agonist, 1 and 5) and JNJ7777120 (H4R antagonist, 10).

Results

Increased HDC gene expression is associated with better relapse-free and overall survival in breast cancer patients. Histamine treatment (5 mg kg−1) of 4T1 tumour-bearing mice reduced tumour growth and increased apoptosis. Although no immunomodulatory effects were observed in wild-type mice, significant correlations between tumour weight and cytotoxic lymphocyte infiltration were detected in H4R knockout mice. H4R agonist or antagonist differentially modulated tumour growth and immunity in 4T1 tumour-bearing mice.

Conclusions

Histamine plays a complex role and stands out as a promising drug for TNBC treatment, which deserves to be tested in clinical settings. HDC expression level is associated with clinicopathological characteristics, suggesting a prognostic value in breast cancer.
Modulation of the extrinsic cell death signaling pathway by viral Flip induces acute-death mediated liver failure
Authors: Bittel Miriam , Kremer Andreas E. , Stürzl Michael , Wirtz Stefan , Stolzer Iris , Neurath Markus F. , Ballon Gianna , Günther Claudia
Published: November 2019

During viral infections viruses express molecules that interfere with the host-cell death machinery and thus inhibit cell death responses. For example the viral FLIP (vFLIP) encoded by Kaposi’s sarcoma-associated herpesvirus interacts and inhibits the central cell death effector, Caspase-8. In order to analyze the impact of anti-apoptotic viral proteins, like vFlip, on liver physiology in vivo, mice expressing vFlip constitutively in hepatocytes (vFlipAlbCre+) were generated. Transgenic expression of vFlip caused severe liver tissue injury accompanied by massive hepatocellular necrosis and inflammation that finally culminated in early postnatal death of mice. On a molecular level, hepatocellular death was mediated by RIPK1-MLKL necroptosis driven by an autocrine TNF production. The loss of hepatocytes was accompanied by impaired bile acid production and disruption of the bile duct structure with impact on the liver-gut axis. Notably, embryonic development and tissue homeostasis were unaffected by vFlip expression. In summary our data uncovered that transgenic expression of vFlip can cause severe liver injury in mice, culminating in multiple organ insufficiency and death. These results demonstrate that viral cell death regulatory molecules exhibit different facets of activities beyond the inhibition of cell death that may merit more sophisticated in vitro and in vivo analysis.
New frontiers to cure Alport syndrome: COL4A3 and COL4A5 gene editing in podocyte-lineage cells
Authors: Daga Sergio , Donati Francesco , Capitani Katia , Croci Susanna , Tita Rossella , Giliberti Annarita , Valentino Floriana , Benetti Elisa , Fallerini Chiara , Niccheri Francesca , Baldassarri Margherita , Mencarelli Maria Antonietta , Frullanti Elisa , Furini Simone , Conticello Silvestro Giovanni , Renieri Alessandra , Pinto Anna Maria
Published: November 2019

Alport syndrome (AS) is an inherited genetic disorder characterized by range of alterations from glomerular basement membrane abnormalities up to end-stage renal disease. Pathogenic variants in the collagen α3, α4, and α5 encoding genes are causative both of the autosomal dominant and of the X-linked forms of AS. Podocytes are the only renal cells that are able to produce the COL(IV)a3-a4a5 heterotrimer. We have previously demonstrated how it is possible to isolate podocyte-lineage cells from urine of patients, providing an easily accessible cellular model closer to the podocytes’ physiological conditions. Taking advantage of disease-relevant cell lines, we employed a two-plasmid approach in order to achieve a beneficial and stable variant-specific correction using CRISPR/Cas9 genome editing. One plasmid carries a Donor DNA and a reporter system mCherry/GFP to track the activity of Cas9 in cells. The other plasmid carries a self-cleaving SpCas9 and the variant-specific sgRNA. We have analyzed two stable podocyte-lineage cell lines, harboring a variant in the X-linked COL4A5 (p.(Gly624Asp)) and in the autosomal COL4A3 gene (p.(Gly856Glu)). We have achieved reversion of variants greater than 40% with undesired insertions/deletions lower than 15%. Overall, we have demonstrated a new gene therapy approach directly on patients’ cells, key players of Alport pathogenesis, and we have reverted COL4 causative variants towards the wild type state. These results, in combination with preclinical models, could open new frontiers in the management and the treatment of the disorder.
In situ mapping of activity distribution and oxygen evolution reaction in vanadium flow batteries
Authors: Ma Kaijie , Zhang Yunong , Liu Le , Xi Jingyu , Qiu Xinping , Guan Tian , He Yonghong
Published: November 2019

Understanding spatial distribution difference and reaction kinetics of the electrode is vital for enhancing the electrochemical reaction efficiency. Here, we report a total internal reflection imaging sensor without background current interference to map local current distribution of the electrode in a vanadium redox flow battery during cyclic voltammetry (CV), enabling mapping of the activity and reversibility distribution with the spatial resolution of a single fiber. Three graphite felts with different activity are compared to verify its feasibility. In long-term cyclic voltammetry, the oxygen evolution reaction is proved to enhance activity distribution, and homogeneity of the electrode and its bubble kinetics with periodic fluctuation is consistent with the cyclic voltammetry curve, enabling the onset oxygen evolution/reduction potential determination. Higher activity and irreversibility distribution of the electrode is found in favor of the oxygen evolution reaction. This sensor has potential to detect in situ, among other processes, electrochemical reactions in flow batteries, water splitting, electrocatalysis and electrochemical corrosion.
Evidence of reactivation of a hydrothermal system from seismic anisotropy changes
Authors: Saade Maria , Araragi Kohtaro , Montagner Jean Paul , Kaminski Edouard , Roux Philippe , Aoki Yosuke , Brenguier Florent
Published: November 2019

Seismic velocity measurements have revealed that the Tohoku-Oki earthquake affected velocity structures of volcanic zones far from the epicenter. Using a seismological method based on ambient seismic noise interferometry, we monitored the anisotropy in the Mount Fuji area during the year 2011, in which the Tohoku-Oki earthquake occurred (Mw = 9.0). Here we show that even at 400 km from the epicenter, temporal variations of seismic anisotropy were observed. These variations can be explained by changes in the alignment of cracks or fluid inclusions beneath the volcanic area due to stress perturbations and the propagation of a hydrothermal fluid surge beneath the Hakone hydrothermal volcanic area. Our results demonstrate how a better understanding of the origin of anisotropy and its temporal changes beneath volcanoes and in the crust can provide insight into active processes, and can be used as part of a suite of volcanic monitoring and forecasting tools.
Genome-wide associated study identifies NAC42-activated nitrate transporter conferring high nitrogen use efficiency in rice
Authors: Tang Weijie , Ye Jian , Yao Xiangmei , Zhao Pingzhi , Xuan Wei , Tian Yunlu , Zhang Yuanyan , Xu Shuang , An Hongzhou , Chen Gaoming , Yu Jun , Wu Wei , Ge Yuwei , Liu Xiaolan , Li Jin , Zhang Hanzhi , Zhao Yaqin , Yang Bing , Jiang Xingzhou , Peng Chao , Zhou Cong , Terzaghi William , Wang Chunming , Wan Jianmin
Published: November 2019

Over-application of nitrogen fertilizer in fields has had a negative impact on both environment and human health. Domesticated rice varieties with high nitrogen use efficiency (NUE) reduce fertilizer for sustainable agriculture. Here, we perform genome-wide association analysis of a diverse rice population displaying extreme nitrogen-related phenotypes over three successive years in the field, and identify an elite haplotype of nitrate transporter OsNPF6.1HapB that enhances nitrate uptake and confers high NUE by increasing yield under low nitrogen supply. OsNPF6.1HapB differs in both the protein and promoter element with natural variations, which are differentially trans-activated by OsNAC42, a NUE-related transcription factor. The rare natural allele OsNPF6.1HapB, derived from variation in wild rice and selected for enhancing both NUE and yield, has been lost in 90.3% of rice varieties due to the increased application of fertilizer. Our discovery highlights this NAC42-NPF6.1 signaling cascade as a strategy for high NUE and yield breeding in rice.
Symmetry of molecular Rydberg states revealed by XUV transient absorption spectroscopy
Authors: Peng Peng , Marceau Claude , Hervé Marius , Corkum P. B. , Naumov A. Yu. , Villeneuve D. M.
Published: November 2019

Transient absorption spectroscopy is utilized extensively for measurements of bound- and quasibound-state dynamics of atoms and molecules. The extension of this technique into the extreme ultraviolet (XUV) region with attosecond pulses has the potential to attain unprecedented time resolution. Here we apply this technique to aligned-in-space molecules. The XUV pulses are much shorter than the time during which the molecules remain aligned, typically$$<$$<100 fs. However, transient absorption is not an instantaneous probe, because long-lived coherences re-emit for picoseconds to nanoseconds. Due to dephasing of the rotational wavepacket, it is not clear if these coherences will be evident in the absorption spectrum, and whether the properties of the initial excitations will be preserved. We studied Rydberg states of N$${}_{2}$$2and O$${}_{2}$$2from 12 to 23 eV. We were able to determine the polarization direction of the electronic transitions, and hence identify the symmetry of the final states.
Global geochemical fingerprinting of plume intensity suggests coupling with the supercontinent cycle
Authors: Gamal EL Dien Hamed , Doucet Luc S. , Li Zheng-Xiang , Cox Grant , Mitchell Ross
Published: November 2019

Plate tectonics and mantle plumes are two of the most fundamental solid-Earth processes that have operated through much of Earth history. For the past 300 million years, mantle plumes are known to derive mostly from two large low shear velocity provinces (LLSVPs) above the core-mantle boundary, referred to as the African and Pacific superplumes, but their possible connection with plate tectonics is debated. Here, we demonstrate that transition elements (Ni, Cr, and Fe/Mn) in basaltic rocks can be used to trace plume-related magmatism through Earth history. Our analysis indicates the presence of a direct relationship between the intensity of plume magmatism and the supercontinent cycle, suggesting a possible dynamic coupling between supercontinent and superplume events. In addition, our analysis shows a consistent sudden drop in MgO, Ni and Cr at ~3.2–3.0 billion years ago, possibly indicating an abrupt change in mantle temperature at the start of global plate tectonics.
Leishmania RNA virus exacerbates Leishmaniasis by subverting innate immunity via TLR3-mediated NLRP3 inflammasome inhibition
Authors: de Carvalho Renan V. H. , Lima-Junior Djalma S. , da Silva Marcus Vinícius G. , Dilucca Marisa , Rodrigues Tamara S. , Horta Catarina V. , Silva Alexandre L. N. , da Silva Patrick F. , Frantz Fabiani G. , Lorenzon Lucas B. , Souza Marcos Michel , Almeida Fausto , Cantanhêde Lilian M. , Ferreira Ricardo de Godoi M. , Cruz Angela K. , Zamboni Dario S.
Published: November 2019

Leishmania RNA virus (LRV) is an important virulence factor associated with the development of mucocutaneous Leishmaniasis, a severe form of the disease. LRV-mediated disease exacerbation relies on TLR3 activation, but downstream mechanisms remain largely unexplored. Here, we combine human and mouse data to demonstrate that LRV triggers TLR3 and TRIF to induce type I IFN production, which induces autophagy. This process results in ATG5-mediated degradation of NLRP3 and ASC, thereby limiting NLRP3 inflammasome activation in macrophages. Consistent with the known restricting role of NLRP3 for Leishmania replication, the signaling pathway triggered by LRV results in increased parasite survival and disease progression. In support of this data, we find that lesions in patients infected with LRV+ Leishmania are associated with reduced inflammasome activation and the development of mucocutaneous disease. Our findings reveal the mechanisms triggered by LRV that contribute to the development of the debilitating mucocutaneous form of Leishmaniasis.
Deep ocean seascape and Pseudotanaidae (Crustacea: Tanaidacea) diversity at the Clarion-Clipperton Fracture Zone
Authors: Jakiel Aleksandra , Palero Ferran , Błażewicz Magdalena
Published: November 2019

Understanding the diversity and spatial distribution of benthic species is fundamental to properly assess the impact of deep sea mining. Tanaidacea provide an exceptional opportunity for assessing spatial patterns in the deep-sea, given their low mobility and limited dispersal potential. The diversity and distribution of pseudotanaid species is characterized here for the Clarion and Clipperton Fractures Zone (CCZ), which is the most extensive deposit field of metallic nodules. Samples were taken from the Belgian, German and French license areas, but also from the APEI 3 (Area of Particular Environmental Interest 3) of the Interoceanmetal consortium associates. The combination of morphological and genetic data uncovered one new pseudotanaid genus (Beksitanais n. gen.) and 14 new species of Pseudotanais (2 of them virtual taxa). Moreover, our results suggest that spatial structuring of pseudotanaid diversity is correlated with deep-sea features, particularly the presence of fractures and seamount chains crossing the CCZ. The presence of geographical barriers delimiting species distributions has important implications for the establishment of protected areas, and the APEI3 protected area contains only one third of the total pseudotanaid species in CCZ. The specimen collection studied here is extremely valuable and represents an important first step in characterizing the diversity and distribution of pseudotanaids within the Tropical Eastern Pacific.
Methodological aspects of testing vestibular evoked myogenic potentials in infants at universal hearing screening program
Authors: Verrecchia Luca , Karpeta Niki , Westin Magnus , Johansson Ann , Aldenklint Sonny , Brantberg Krister , Duan Maoli
Published: November 2019

Motor development in infants is dependent upon the function of the inner ear balance organ (vestibular organ). Vestibular failure causes motor delays in early infancy and suboptimal motor skills later on. A vestibular test for newborns and infants that is applicable on a large scale, safe and cost effective is in demand in various contexts: in the differential diagnosis of early onset hearing loss to determine forms associated with vestibular failure; in early hearing habilitation with cochlear implant, indicating the vestibular predominant side; and in the habilitation of children affected by motor skill disorders, revealing the contribution of a vestibular failure. This work explored the feasibility of cervical vestibular evoked myogenic potentials (VEMP) in conjunction with newborn universal hearing screening program. VEMP was measured after the hearing tests and was evoked by bone-conducted stimuli. Moreover, stimulus delivery was regulated by neck muscle activity, with infants rested unconstrained in their parents´ arms and with the head supported by the operator´s hand. This VEMP protocol showed a high level of feasibility in terms of test viability and result reproducibility. VEMP integrated into the newborn hearing screening program may represent a practical method for large-scale assessment of balance function in infants.
Serine substitutions are linked to codon usage and differ for variable and conserved protein regions
Authors: Schwartz Gregory W. , Shauli Tair , Linial Michal , Hershberg Uri
Published: November 2019

Serine is the only amino acid that is encoded by two disjoint codon sets (TCN & AGY) so that a tandem substitution of two nucleotides is required to switch between the two sets. We show that these codon sets underlie distinct substitution patterns at positions subject to purifying and diversifying selections. We found that in humans, positions that are conserved among ~100 vertebrates, and thus subjected to purifying selection, are enriched for substitutions involving serine (TCN, denoted S′), proline, and alanine, (S′PA). In contrast, the less conserved positions are enriched for serine encoded with AGY codons (denoted S″), glycine and asparagine, (GS″N). We tested this phenomenon in the HIV envelope glycoprotein (gp120), and the V-gene that encodes B-cell receptors/antibodies. These fast evolving proteins both have hypervariable positions, which are under diversifying selection, closely adjacent to highly conserved structural regions. In both instances, we identified an opposite abundance of two groups of serine substitutions, with enrichment of S′PA in the conserved positions, and GS″N in the hypervariable regions. Finally, we analyzed the substitutions across 60,000 individual human exomes to show that, when serine has a specific functional constraint of phosphorylation capability, S′ codons are 32-folds less prone than S″ to substitutions to Threonine or Tyrosine that could potentially retain the phosphorylation site capacity. Combined, our results, that cover evolutionary signals at different temporal scales, demonstrate that through its encoding by two codon sets, serine allows for the existence of alternating substitution patterns within positions of functional maintenance versus sites of rapid diversification.
Treatment with etanercept and low monocyte concentration contribute to the risk of invasive aspergillosis in patients post allogeneic stem cell transplantation
Authors: Zoran Tamara , Weber Michael , Springer Jan , White P. Lewis , Bauer Joachim , Schober Annika , Löffler Claudia , Seelbinder Bastian , Hünniger Kerstin , Kurzai Oliver , Scherag André , Schäuble Sascha , Morton C. Oliver , Einsele Hermann , Linde Jörg , Löffler Jürgen
Published: November 2019

Invasive aspergillosis (IA) is a life-threatening complication among allogeneic hematopoietic stem cell transplant (alloSCT) recipients. Despite well known risk factors and different available assays, diagnosis of invasive aspergillosis remains challenging. 103 clinical variables from patients with hematological malignancies and subsequent alloSCT were collected. Associations between collected variables and patients with (n = 36) and without IA (n = 36) were investigated by applying univariate and multivariable logistic regression. The predictive power of the final model was tested in an independent patient cohort (23 IA cases and 25 control patients). Findings were investigated further byin vitrostudies, which analysed the effect of etanercept onA. fumigatus-stimulated macrophages at the gene expression and cytokine secretion. Additionally, the release of C-X-C motif chemokine ligand 10 (CXCL10) in patient sera was studied. Low monocyte concentration (p = 4.8 × 10−06), severe GvHD of the gut (grade 2–4) (p = 1.08 × 10−02) and etanercept treatment of GvHD (p = 3.5 × 10−03) were significantly associated with IA. Our studies showed that etanercept lowers CXCL10 concentrationsin vitroandex vivoand down-regulates genes involved in immune responses and TNF-alpha signaling. Our study offers clinicians new information regarding risk factors for IA including low monocyte counts and administration of etanercept. After necessary validation, such information may be used for decision making regarding antifungal prophylaxis or closely monitoring patients at risk.
The SMYD3 methyltransferase promotes myogenesis by activating the myogenin regulatory network
Authors: Codato Roberta , Perichon Martine , Divol Arnaud , Fung Ella , Sotiropoulos Athanassia , Bigot Anne , Weitzman Jonathan B. , Medjkane Souhila
Published: November 2019

The coordinated expression of myogenic regulatory factors, including MyoD and myogenin, orchestrates the steps of skeletal muscle development, from myoblast proliferation and cell-cycle exit, to myoblast fusion and myotubes maturation. Yet, it remains unclear how key transcription factors and epigenetic enzymes cooperate to guide myogenic differentiation. Proteins of the SMYD (SET and MYND domain-containing) methyltransferase family participate in cardiac and skeletal myogenesis during development in zebrafish, Drosophila and mice. Here, we show that the mammalian SMYD3 methyltransferase coordinates skeletal muscle differentiation in vitro. Overexpression of SMYD3 in myoblasts promoted muscle differentiation and myoblasts fusion. Conversely, silencing of endogenous SMYD3 or its pharmacological inhibition impaired muscle differentiation. Genome-wide transcriptomic analysis of murine myoblasts, with silenced or overexpressed SMYD3, revealed that SMYD3 impacts skeletal muscle differentiation by targeting the key muscle regulatory factor myogenin. The role of SMYD3 in the regulation of skeletal muscle differentiation and myotube formation, partially via the myogenin transcriptional network, highlights the importance of methyltransferases in mammalian myogenesis.
Effective CRISPR interference of an endogenous gene via a single transgene in mice
Authors: MacLeod Ryan S. , Cawley Keisha M. , Gubrij Igor , Nookaew Intawat , Onal Melda , O’Brien Charles A.
Published: November 2019

Drawbacks of conditional gene deletion in mice include the need for extensive breeding and, often, a lack of cell type-specificity. CRISPR interference (CRISPRi) is an alternative approach for loss-of-function studies that inhibits expression by guiding a transcriptional repressor to the transcription start-site of target genes. However, there has been limited exploration of CRISPRi in mice. We tested the effectiveness of a single CRISPRi transgene broadly expressing a single guide RNA and a catalytically dead Cas9 fused to the KRAB repressor domain to suppress a well-characterized target gene, Tnfsf11. The phenotype of CRISPRi transgenic mice was compared to mice with germline deletion of Tnfsf11, which are osteopetrotic and do not form lymph nodes. High transgene expression mimicked gene deletion, with failure of lymph node development and classic signs of osteopetrosis such as high bone mass and failure of tooth eruption. Mice with low transgene expression were normal and mice with medium expression displayed an intermediate phenotype. Transgene expression in tissues from these mice correlated inversely with Tnfsf11 mRNA levels. These results demonstrate that a single CRISPRi transgene can effectively suppress a target gene in mice and suggest that this approach may be useful for cell type-specific loss-of-function studies.
Effect of electric field on optoelectronic properties of indiene monolayer for photoelectric nanodevices
Authors: Singh Deobrat , Gupta Sanjeev K. , Lukačević Igor , Mužević Matko , Sonvane Yogesh , Ahuja Rajeev
Published: November 2019

In recent years, layered materials display interesting properties and the quest for new sorts of two-dimensional (2D) structures is a significance for future device manufacture. In this paper, we study electronic and optical properties of 2D indiene allotropes with planar and buckled structures. The optical properties calculations are based on density functional theory (DFT) simulations including in-plane and out-of-plane directions of light polarization. We indicate that the optical properties such as complex refractive index, absorption spectrum, electron energy loss function (EELS), reflectivity and optical conductivity spectra are strongly dependent on the direction of light’s polarization. High values and narrow peaks in optical spectra introduce indiene to the field of ultra-thin optical systems. The effect of external static electric field on electronic and optical properties of indiene is also observed and discussed. We show that the band gap in buckled indiene can be effectively changed by applying the external electric field. The discoveries here expand the group of 2D materials beyond graphene and transition metal dichalcogenides (TMDs) and give valuable data for future experimental realization of new mono-elemental materials with conceivable applications in optical devices.
Breakthrough in Marine Invertebrate Cell Culture: Sponge Cells Divide Rapidly in Improved Nutrient Medium
Authors: Conkling Megan , Hesp Kylie , Munroe Stephanie , Sandoval Kenneth , Martens Dirk E. , Sipkema Detmer , Wijffels Rene H. , Pomponi Shirley A.
Published: November 2019

Sponges (Phylum Porifera) are among the oldest Metazoa and considered critical to understanding animal evolution and development. They are also the most prolific source of marine-derived chemicals with pharmaceutical relevance. Cell lines are important tools for research in many disciplines, and have been established for many organisms, including freshwater and terrestrial invertebrates. Despite many efforts over multiple decades, there are still no cell lines for marine invertebrates. In this study, we report a breakthrough: we demonstrate that an amino acid-optimized nutrient medium stimulates rapid cell division in 9 sponge species. The fastest dividing cells doubled in less than 1 hour. Cultures of 3 species were subcultured from 3 to 5 times, with an average of 5.99 population doublings after subculturing, and a lifespan from 21 to 35 days. Our results form the basis for developing marine invertebrate cell models to better understand early animal evolution, determine the role of secondary metabolites, and predict the impact of climate change to coral reef community ecology. Furthermore, sponge cell lines can be used to scale-up production of sponge-derived chemicals for clinical trials and develop new drugs to combat cancer and other diseases.
Dissection of major cancer gene variants in subsets of circulating tumor cells in advanced breast cancer
Authors: D’Oronzo Stella , Lovero Domenica , Palmirotta Raffaele , Stucci Luigia Stefania , Tucci Marco , Felici Claudia , Cascardi Eliano , Giardina Carmela , Cafforio Paola , Silvestris Franco
Published: November 2019

Enumeration of circulating tumor cells (CTCs) may reflect the metastatic potential of breast cancer (BC). By using the DEPArray, we investigated CTCs with respect to their epithelial-to-mesenchymal transition phenotype and compared their genomic heterogeneity with tissue biopsies. Seventeen stage IV BC patients were enrolled. Pre-enriched CTC suspensions were stained with fluorescent-labeled antibodies to epithelial (E) and mesenchymal (M) markers. CTC samples were processed by DEPArray system and clustered in relation to their markers. DNA from CTCs, as well as from primary tumor samples, was sequenced by next generation sequencing to assess the mutational state of 50 major cancer-related genes. We identified four different CTC subsets that harbored different gene variants. The most heterogenous CTC subsets included the M+/E− phenotype, which, however, expressed only 7 repeatedly mutated genes, while in the M−/E+ subset multiple mutations affected only 2 out of 50 genes. When matching all gene variants among CTC subsets, a small number of mutations was shared by only 4 genes, namely ATM, FGFR3, PIK3CA, and TP53 that, however, were absent in primary tumors. Our results postulate that the detected mutations in all CTC subsets may be considered as genomic markers of metastatic dissemination to be investigated during early stages of BC.
Untargeted histone profiling during naive conversion uncovers conserved modification markers between mouse and human
Authors: De Clerck Laura , Taelman Jasin , Popovic Mina , Willems Sander , Van der Jeught Margot , Heindryckx Björn , De Sutter Petra , Marks Hendrik , Deforce Dieter , Dhaenens Maarten
Published: November 2019

Recent progress has enabled the conversion of primed human embryonic stem cells (hESCs) to the naive state of pluripotency, resembling the well-characterized naive mouse ESCs (mESCs). However, a thorough histone epigenetic characterization of this conversion process is currently lacking, while its likeness to the mouse model has not been clearly established. Here, we profile the histone epigenome of hESCs during conversion in a time-resolved experimental design, using an untargeted mass spectrometry-based approach. In total, 23 histone post-translational modifications (hPTMs) changed significantly over time. H3K27Me3 was the most prominently increasing marker hPTM in naive hESCs. This is in line with previous reports in mouse, prompting us to compare all the shared hPTM fold changes between mouse and human, revealing a set of conserved hPTM markers for the naive state. Principally, we present the first roadmap of the changing human histone epigenome during the conversion of hESCs from the primed to the naive state. This further revealed similarities with mouse, which hint at a conserved mammalian epigenetic signature of the ground state of pluripotency.
New insight into the mechanisms of ectopic fat deposition improvement after bariatric surgery
Authors: Angelini Giulia , Castagneto Gissey Lidia , Del Corpo Giulia , Giordano Carla , Cerbelli Bruna , Severino Anna , Manco Melania , Basso Nicola , Birkenfeld Andreas L. , Bornstein Stefan R. , Genco Alfredo , Mingrone Geltrude , Casella Giovanni
Published: November 2019

Non-alcoholic fatty-liver disease (NAFLD) is frequent in obese patients and represents a major risk factor for the development of diabetes and its complications. Bariatric surgery reverses the hepatic features of NAFLD. However, its mechanism of action remains elusive. We performed a comprehensive analysis of the mechanism leading to the improvement of NAFLD and insulin resistance in both obese rodents and humans following sleeve-gastrectomy (SG). SG improved insulin sensitivity and reduced hepatic and monocyte fat accumulation. Importantly, fat accumulation in monocytes was well comparable to that in hepatocytes, suggesting that Plin2 levels in monocytes might be a non-invasive marker for the diagnosis of NAFLD. Both in vitro and in vivo studies demonstrated an effective metabolic regeneration of liver function and insulin sensitivity. Specifically, SG improved NAFLD significantly by enhancing AMP-activated protein kinase (AMPK) phosphorylation and chaperone-mediated autophagy (CMA) that translate into the removal of Plin2 coating lipid droplets. This led to an increase in lipolysis and specific amelioration of hepatic insulin resistance. Elucidating the mechanism of impaired liver metabolism in obese subjects will help to design new strategies for the prevention and treatment of NAFLD.
Small behavioral adaptations enable more effective prey capture by producing 3D-structured spider threads
Authors: Grannemann Caroline C. F. , Meyer Marco , Reinhardt Marian , Ramírez Martín J. , Herberstein Marie E. , Joel Anna-Christin
Published: November 2019

Spiders are known for producing specialized fibers. The radial orb-web, for example, contains tough silk used for the web frame and the capture spiral consists of elastic silk, able to stretch when prey impacts the web. In concert, silk proteins and web geometry affects the spider’s ability to capture prey. Both factors have received considerable research attention, but next to no attention has been paid to the influence of fiber processing on web performance. Cribellate spiders produce a complex fiber alignment as their capture threads. With a temporally controlled spinneret movement, they connect different fibers at specific points to each other. One of the most complex capture threads is produced by the southern house spider, Kukulcania hibernalis (Filistatidae). In contrast to the so far characterized linear threads of other cribellate spiders, K. hibernalis spins capture threads in a zigzag pattern due to a slightly altered spinneret movement. The resulting more complex fiber alignment increased the thread’s overall ability to restrain prey, probably by increasing the adhesion area as well as its extensibility. Kukulcania hibernalis' cribellate silk perfectly illustrates the impact of small behavioral differences on the thread assembly and, thus, of silk functionality.
Snow-dirt sludge as an indicator of environmental and sedimentation processes in the urban environment
Authors: Seleznev Andrian , Yarmoshenko Ilia , Malinovsky Georgy , Ilgasheva Ekaterina , Baglaeva Elena , Ryanskaya Anastasia , Kiseleva Daria , Gulyaeva Tamara
Published: November 2019

The formation of snow-dirt sludge (SDS) via the mixing of snow and surface-deposited sediment by vehicles and pedestrians is one of the least studied sedimentation processes in urban areas. The aim of this study was to analyse the material, mineral, particle size, and chemical compositions of the SDS solid phase. The study was conducted using Ekaterinburg, Russia, as an example city with an intense anthropogenic impact and a long cold snowy period. The average content of the SDS solid phase was approximately 35 g L−1 of meltwater on heavy traffic roads, of which the dust fraction (<0.1 mm) accounted for 23 g L−1. On driveways and lawns, the contents of the SDS solid phase were 12 and 6.6 g L−1, respectively. The mineral composition of the SDS solid phase was generally similar to the geology of the surrounding area, which is composed of a mosaicked combination of felsic and mafic complexes. The presence of building material fragments and other anthropogenic particles confirms the significant anthropogenic impact. The chemical composition contained major and minor elements specific to the minerals and materials that constitute the SDS solid phase. There was significant variability in the concentrations of Pb, Cu, and Zn in the granulometric fractions, indicating pollution. Intensive melting of SDS with a high particulate matter (PM) content is an important factor influencing the environmental quality of the urban environment.