bluuebunny/crossref_metadata_2025 huggingface dataset:
The Contribution of Symbiodinium Microadriaticum to the Symbiosome Membrane in the Anthozoan Host Aiptasia Pallida
Authors: Wakefield Timothy S , Kempf Stephen C , Farmer Mark A
Published: July 2020

Most endosymbionts remain separated from their host cell by a derivative of the phagocytic membrane. This membrane and its contents have been defined as a novel “organelle-like” structure called a symbiosome. However, in the case of many cnidarian-dinoflagellate symbioses the putative symbiosome is composed of multiple layers of apparent membranes (Fig. 1). In the past the origin of these membranes has been assigned to host and/or symbiont with very little experimental evidence to support either view; however, several interesting hypotheses have been proposed to explain the origin of the “membranes”. Trench and Blank suggest that occasionally the outer most layer of the vegetative symbiont's cell wall is sloughed off the surface of the cell. They concede that the outer most layer of “membranes” must be the host vacuolar membrane, but believe that it simply prevents the sloughed layer from moving away from the cell, (as would happen in culture), and that, over time, multiple sloughed layers accumulate beneath the host vacular membrane.
Amino Acid Composition and Immunolabelling of a 42.5 KDA Protein from Phloem Exudate of Luffa Cylindrica Fruits
Authors: Wang M C , Chen Y R
Published: July 2020

Phloem proteins are specifically presented in phloem tissues of monocotyledons and dicotyledons. Ultrastructural studies showed that they were filamentous, spherical, tubular, crystalline and amorphous in shaped They were present in the sieve elements and sometimes are also found in companion cells and phloem parenchyma cells. The diversities in shape and biogenesis of plant p-protein in relation to plant species and developmental stage of phloem tissues were reported. In the present study, a 42.5 kDA protein obtained from phloem exudate of Luffa cylindrica fruits were examined with amino acid composition, immnoblotting, and immunolocalization.

Phloem exudates leaking from Luffa cylindrica fruits by a simple razor blade cutting were mixed with the extraction medium containing antioxidant and rapidly separated by 2-dimensional gel of native and sodium dodecylsulfate (SDS) polyacrylamide gel electrophoresis (PAGE).
Fast Pixelated Detectors in Scanning Transmission Electron Microscopy. Part I: Data Acquisition, Live Processing, and Storage
Authors: Nord Magnus , Webster Robert W. H. , Paton Kirsty A. , McVitie Stephen , McGrouther Damien , MacLaren Ian , Paterson Gary W.
Published: July 2020

The use of fast pixelated detectors and direct electron detection technology is revolutionizing many aspects of scanning transmission electron microscopy (STEM). The widespread adoption of these new technologies is impeded by the technical challenges associated with them. These include issues related to hardware control, and the acquisition, real-time processing and visualization, and storage of data from such detectors. We discuss these problems and present software solutions for them, with a view to making the benefits of new detectors in the context of STEM more accessible. Throughout, we provide examples of the application of the technologies presented, using data from a Medipix3 direct electron detector. Most of our software are available under an open source licence, permitting transparency of the implemented algorithms, and allowing the community to freely use and further improve upon them.
Simultaneous Three-Dimensional Vascular and Tubular Imaging of Whole Mouse Kidneys With X-ray μCT
Authors: Kuo Willy , Le Ngoc An , Spingler Bernhard , Wenger Roland H. , Kipar Anja , Hetzel Udo , Schulz Georg , Müller Bert , Kurtcuoglu Vartan
Published: July 2020

Concurrent three-dimensional imaging of the renal vascular and tubular systems on the whole-kidney scale with capillary level resolution is labor-intensive and technically difficult. Approaches based on vascular corrosion casting and X-ray micro computed tomography (μCT), for example, suffer from vascular filling artifacts and necessitate imaging with an additional modality to acquire tubules. In this work, we report on a new sample preparation, image acquisition, and quantification protocol for simultaneous vascular and tubular μCT imaging of whole, uncorroded mouse kidneys. The protocol consists of vascular perfusion with the water-soluble, aldehyde-fixable, polymeric X-ray contrast agent XlinCA, followed by laboratory-source μCT imaging and structural analysis using the freely available Fiji/ImageJ software. We achieved consistent filling of the entire capillary bed and staining of the tubules in the cortex and outer medulla. After imaging at isotropic voxel sizes of 3.3 and 4.4μm, we segmented vascular and tubular systems and quantified luminal volumes, surface areas, diffusion distances, and vessel path lengths. This protocol permits the analysis of vascular and tubular parameters with higher reliability than vascular corrosion casting, less labor than serial sectioning and leaves tissue intact for subsequent histological examination with light and electron microscopy.
Recognizing Sample-Selection Bias in Historical Data
Authors: Zimran Ariell
Published: July 2020

Recent research has ignited a debate in social science history over whether and how to draw conclusions for whole populations from sources that describe only select subsets of these populations. The idiosyncratic availability and survival of historical sources create a threat of sample-selection bias—an error that arises when there are systematic differences between the observed sample and the population of interest. This danger is common in studying trends in health as measured by average stature—scholars can often observe these trends only for soldiers and other similar groups; but whether these patterns are representative of those of the broader population is unclear. This article illustrates what simple patterns in a potentially selected sample can be used to recognize the presence of sample-selection bias in a source, and to understand how such bias might affect conclusions drawn from this source. Applying this intuition to the use of military data to describe stature in the antebellum United States, I present several simple empirical exercises based on these patterns. Finally, I use the results of these exercises to describe how sample-selection bias might affect the use of these data in testing for differences in average stature between the Northeast and the Midwest.
Cognitive Impairment in Old Age
Authors: Di Nuovo Santo , De Beni Rossana , Borella Erika , Marková Hana , Laczó Jan , Vyhnálek Martin
Published: July 2020

Abstract. A decline in cognitive functioning is part of physiological aging. Accelerated cognitive decline is frequently linked to pathological changes, mostly due to Alzheimer’s Disease (AD), but is present also in Mild Cognitive Impairment (MCI) which is a predictor of transition to dementia. This review aims to summarize possible preventive biological and psychological treatments in different stages of lifespan to avoid more rapid cognitive decline and prevent pathological aging. Psychophysiological approaches aim to prevent brain damage and inflammation, two factors playing probably a major role in middle and old age. Interventions on working memory and imagery, using “cognitive reserve,” are beneficial for tolerating neuropathological age-related changes. Some controversial results are outlined, suggesting explanations for the inconsistency of findings. Although clear evidence from interventional studies is lacking, it seems that multi-domain interventions should be recommended to avoid or delay cognitive decline.
Sleep Quality and Daytime Functioning in Older European Adults
Authors: Košćec Bjelajac Adrijana , Holzinger Brigitte , Despot Lučanin Jasminka , Delale Eva Anđela , Lučanin Damir
Published: July 2020

Abstract. The aim of this article was to review research studies related to the issues of sleep in older adults, examining the relationship between sleep quality and a set of psychological variables of daytime functioning in healthy older adults: quality of life, subjective health, functional ability, cognitive function, and emotional state, in Europe. Combined scoping review search strategies resulted in a total of 84 articles selected for review. We conclude there is a considerable amount of European research on sleep quality and its correlates in older adults’ population. Studying these relationships may be the basis for the targeted planning of psychological interventions aiming at raising the quality of life in older adults. The selected domains of older adults’ everyday functioning were all well represented in the retrieved research studies.
Coupled Time‐Lapse Full‐Waveform Inversion for Subsurface Flow Problems Using Intrusive Automatic Differentiation
Authors: Li Dongzhuo , Xu Kailai , Harris Jerry M. , Darve Eric
Published: July 2020

We describe a novel framework for estimating subsurface properties, such as rock permeability and porosity, from time‐lapse observed seismic data by coupling full‐waveform inversion (FWI), subsurface flow processes, and rock physics models. For the inverse modeling, we handle the back propagation of gradients by an intrusive automatic differentiation strategy that offers three levels of user control: (1) At the wave physics level, we adopted the discrete adjoint method in order to use our existing high‐performance FWI code; (2) at the rock physics level, we used built‐in automatic differentiation operators from the TensorFlow backend; (3) at the flow physics level, we implemented customized partial differential equation (PDE) operators for the multiphase flow equations. The three‐level coupled inversion strategy strikes a good balance between computational efficiency and programming efforts, and when the gradients are chained together, it constitutes a coupled inverse system. Our numerical experiments demonstrate that the three‐level coupled inverse problem is superior in terms of accuracy to a traditional decoupled inversion strategy. Additionally, our method is able to simultaneously invert for parameters in empirical relationships such as the rock physics models. Our proposed inverted model can be used for reservoir performance prediction and reservoir management/optimization purposes.
Subduction Initiation by Plume‐Plateau Interaction: Insights From Numerical Models
Authors: Baes Marzieh , Sobolev Stephan V. , Gerya Taras , Brune Sascha
Published: July 2020

It has recently been demonstrated that the interaction of a mantle plume with sufficiently old oceanic lithosphere can initiate subduction. However, the existence of large lithospheric heterogeneities, such as a buoyant plateau, in proximity to a rising plume head may potentially hinder the formation of a new subduction zone. Here, we investigate this scenario by means of 3‐D numerical thermomechanical modeling. We explore how plume‐lithosphere interaction is affected by lithospheric age, relative location of plume head and plateau border, and the strength of the oceanic crust. Our numerical experiments suggest four different geodynamic regimes: (a) oceanic trench formation, (b) circular oceanic‐plateau trench formation, (c) plateau trench formation, and (d) no trench formation. We show that regardless of the age and crustal strength of the oceanic lithosphere, subduction can initiate when the plume head is either below the plateau border or at a distance less than the plume radius from the plateau edge. Crustal heterogeneity facilitates subduction initiation of old oceanic lithosphere. High crustal strength hampers the formation of a new subduction zone when the plume head is located below a young lithosphere containing a thick and strong plateau. We suggest that plume‐plateau interaction in the western margin of the Caribbean could have resulted in subduction initiation when the plume head impinged onto the oceanic lithosphere close to the border between plateau and oceanic crust.
Ionospheric and Magnetic Signatures of a Space Weather Event on 25–29 August 2018: CME and HSSWs
Authors: Younas W. , Amory‐Mazaudier C. , Khan Majid , Fleury R.
Published: July 2020

We present a study concerning a space weather event on 25–29 August 2018, accounting for its ionospheric and magnetic signatures at low latitudes and midlatitudes. The effects of a storm in several longitudinal sectors (Asia, Africa, America, and the Pacific) have been analyzed using various parameters such as total electron content (TEC), geomagnetic field, and column [O/N2] ratio. Positive ionospheric storms are found in all the longitudinal sectors having its maximum effects in the Asian sector, whereas the negative ionospheric storms have been observed in the summer hemisphere (Northern Hemisphere). A large decrease in [O/N2] ratio in the Northern Hemisphere is a possible cause of the observed negative storm effects. Ionospheric F2 region maximum electron density (NmF2) and TEC have shown a positive correlation during this storm. The study suggests that storm time‐generated wind does not have a uniform planetary extension and mainly affects dayside (America and Pacific) and duskside (Africa) sectors. During the space weather event, we observe an asymmetric variation of the magnetic field as a function of the longitude. On the other hand, the magnetic variations at midlatitudes are found to be symmetric in both hemispheres. A signature of the disturbance dynamo (anti‐Sq circulation) has been observed, mainly at low latitudes. We emphasize that the partial ring current (PRC), estimated by the ASYM‐H magnetic index, must also be taken into account along with the SYM‐H index for a better approximation of ionospheric currents. The study further suggests existence of several electric current cells in the ionosphere, which is consistent with the Blanc‐Richmond model.
Dexmedetomidine promotes the progression of hepatocellular carcinoma through hepatic stellate cell activation
Authors: Chen Peng , Luo Xiaojun , Dai Guanqi , Jiang Yuchuan , Luo Yue , Peng Shuang , Wang Hao , Xie Penghui , Qu Chen , Lin Wenyu , Hong Jian , Ning Xue , Li Aimin
Published: July 2020

Dexmedetomidine (DEX) is an anesthetic that is widely used in the clinic, and it has been reported to exhibit paradoxical effects in the progression of multiple solid tumors. In this study, we sought to explore the mechanism by which DEX regulates hepatocellular carcinoma (HCC) progression underlying liver fibrosis. We determined the effects of DEX on tumor progression in an orthotopic HCC mouse model of fibrotic liver. A coculture system and a subcutaneous xenograft model involving coimplantation of mouse hepatoma cells (H22) and primary activated hepatic stellate cells (aHSCs) were used to study the effects of DEX on HCC progression. We found that in the preclinical mouse model of liver fibrosis, DEX treatment significantly shortened median survival time and promoted tumor growth, intrahepatic metastasis and pulmonary metastasis. The DEX receptor (ADRA2A) was mainly expressed in aHSCs but was barely detected in HCC cells. DEX dramatically reinforced HCC malignant behaviors in the presence of aHSCs in both the coculture system and the coimplantation mouse model, but DEX alone exerted no significant effects on the malignancy of HCC. Mechanistically, DEX induced IL-6 secretion from aHSCs and promoted HCC progression via STAT3 activation. Our findings provide evidence that the clinical application of DEX may cause undesirable side effects in HCC patients with liver fibrosis.
Evolutionary compromises in fungal fitness: hydrophobins can hinder the adverse dispersal of conidiospores and challenge their survival
Authors: Cai Feng , Gao Renwei , Zhao Zheng , Ding Mingyue , Jiang Siqi , Yagtu Civan , Zhu Hong , Zhang Jian , Ebner Thomas , Mayrhofer-Reinhartshuber Michael , Kainz Philipp , Chenthamara Komal , Akcapinar Günseli Bayram , Shen Qirong , Druzhinina Irina S
Published: July 2020

Fungal evolutionary biology is impeded by the scarcity of fossils, irregular life cycles, immortality, and frequent asexual reproduction. Simple and diminutive bodies of fungi develop inside a substrate and have exceptional metabolic and ecological plasticity, which hinders species delimitation. However, the unique fungal traits can shed light on evolutionary forces that shape the environmental adaptations of these taxa. Higher filamentous fungi that disperse through aerial spores produce amphiphilic and highly surface-active proteins called hydrophobins (HFBs), which coat spores and mediate environmental interactions. We exploited a library of HFB-deficient mutants for two cryptic species of mycoparasitic and saprotrophic fungi from the genus Trichoderma (Hypocreales) and estimated fungal development, reproductive potential, and stress resistance. HFB4 and HFB10 were found to be relevant for Trichoderma fitness because they could impact the spore-mediated dispersal processes and control other fitness traits. An analysis in silico revealed purifying selection for all cases except for HFB4 from T. harzianum, which evolved under strong positive selection pressure. Interestingly, the deletion of the hfb4 gene in T. harzianum considerably increased its fitness-related traits. Conversely, the deletion of hfb4 in T. guizhouense led to the characteristic phenotypes associated with relatively low fitness. The net contribution of the hfb4 gene to fitness was found to result from evolutionary tradeoffs between individual traits. Our analysis of HFB-dependent fitness traits has provided an evolutionary snapshot of the selective pressures and speciation process in closely related fungal species.
Spermidine activates RIP1 deubiquitination to inhibit TNF-α-induced NF-κB/p65 signaling pathway in osteoarthritis
Authors: Chen Zhong , Lin Chuang-Xin , Song Bin , Li Chang-Chuan , Qiu Jun-Xiong , Li Shi-Xun , Lin Si-Peng , Luo Wen-Qiang , Fu Yuan , Fang Gui-Bin , Wei-Ping Li , Saw Phei Er , Ding Yue
Published: July 2020

Spermidine has been known to inhibit the production of pro-inflammatory cytokines. However, there are no reports about anti-inflammatory effects of spermidine on osteoarthritis (OA). Herein, we examined whether OA progression could be delayed by intraperitoneal injection (i.p.) of spermidine in the anterior cruciate ligament transection (ACLT) and TNF-α induced arthritis (TIA) mouse models. During the process, human FLS cells (H-FLS) were used to investigate the potential ubiquitination mechanism of spermidine-mediated RIP1 in TNF-α-induced NF-κB/p65 signaling. We found that spermidine attenuated synovitis, cartilage degeneration and osteophyte formation, resulting in substantially lower OARSI scores and TNF-α scores in spermidine-treated ACLT and TIA mice. In terms of the mechanism, 9 μM spermidine did not affect the viability, proliferation, cell cycle and apoptosis of H-FLS, and exerted inhibitory effects by activating CYLD-mediated RIP1 deubiquitination on TNF-α-induced NF-κB/p65 signaling in H-FLS. From these data, we can conclude that spermidine attenuates OA progression by the inhibition of TNF-α-induced NF-κB pathway via the deubiquitination of RIP1 in FLS. Therefore, intake of spermidine could be a potential therapy for preventing OA.
Metabolic and psychiatric effects of acyl coenzyme A binding protein (ACBP)/diazepam binding inhibitor (DBI)
Authors: Joseph Adrien , Moriceau Stéphanie , Sica Valentina , Anagnostopoulos Gerasimos , Pol Jonathan , Martins Isabelle , Lafarge Antoine , Maiuri Maria Chiara , Leboyer Marion , Loftus Josephine , Bellivier Frank , Belzeaux Raoul , Berna Fabrice , Etain Bruno , Capdevielle Delphine , Courtet Philippe , Dubertret Caroline , Dubreucq Julien , Thierry D’. Amato , Fond Guillaume , Gard Sebastien , Llorca Pierre-Michel , Mallet Jasmina , Misdrahi David , Olié Emilie , Passerieux Christine , Polosan Mircea , Roux Paul , Samalin Ludovic , Schürhoff Franck , Schwan Raymond ,   the FACE-SZ and FACE-BD (FondaMental Academic Centers of Expertise, for Schizophrenia and for Bipolar Disorder) Groups, Magnan Christophe , Oury Franck , Bravo-San Pedro José M. , Kroemer Guido
Published: July 2020

Acyl coenzyme A binding protein (ACBP), also known as diazepam binding inhibitor (DBI) is a multifunctional protein with an intracellular action (as ACBP), as well as with an extracellular role (as DBI). The plasma levels of soluble ACBP/DBI are elevated in human obesity and reduced in anorexia nervosa. Accumulating evidence indicates that genetic or antibody-mediated neutralization of ACBP/DBI has anorexigenic effects, thus inhibiting food intake and inducing lipo-catabolic reactions in mice. A number of anorexiants have been withdrawn from clinical development because of their side effects including an increase in depression and suicide. For this reason, we investigated the psychiatric impact of ACBP/DBI in mouse models and patient cohorts. Intravenously (i.v.) injected ACBP/DBI protein conserved its orexigenic function when the protein was mutated to abolish acyl coenzyme A binding, but lost its appetite-stimulatory effect in mice bearing a mutation in the γ2 subunit of the γ-aminobutyric acid (GABA) A receptor (GABAAR). ACBP/DBI neutralization by intraperitoneal (i.p.) injection of a specific mAb blunted excessive food intake in starved and leptin-deficient mice, but not in ghrelin-treated animals. Neither i.v. nor i.p. injected anti-ACBP/DBI antibody affected the behavior of mice in the dark–light box and open-field test. In contrast, ACBP/DBI increased immobility in the forced swim test, while anti-ACBP/DBI antibody counteracted this sign of depression. In patients diagnosed with therapy-resistant bipolar disorder or schizophrenia, ACBP/DBI similarly correlated with body mass index (BMI), not with the psychiatric diagnosis. Patients with high levels of ACBP/DBI were at risk of dyslipidemia and this effect was independent from BMI, as indicated by multivariate analysis. In summary, it appears that ACBP/DBI neutralization has no negative impact on mood and that human depression is not associated with alterations in ACBP/DBI concentrations.
Activating PIK3CA mutation promotes osteogenesis of bone marrow mesenchymal stem cells in macrodactyly
Authors: Cui Hengqing , Han Gang , Sun Bin , Fang Xia , Dai Xinyi , Zhou Shengbo , Mao Hailei , Wang Bin
Published: July 2020

Macrodactyly is a disabling congenital disease characterized by overgrowth of soft tissues and bones, which leads to finger enlargement and joint deformity. The mechanism of bone overgrowth in macrodactyly was rarely understood. In our study bone manifestations of three macrodactyly patients were analyzed by micro-CT. PIK3CA mutation was detected by next-generation sequencing (NGS) of a tumor gene-panel. The PI3K/AKT/mTOR pathway activation and target genes were analyzed. The osteogenic potential of macrodactyly-derived bone marrow mesenchymal stem cells (MAC-BMSCs) was compared with polydactyly-derived bone marrow mesenchymal stem cells (PD-BMSCs). PIK3CA inhibitors were tested for proliferation and osteogenesis potential of MAC-BMSCs. Activating PIK3CA mutations and activation of PI3K/AKT/mTOR pathway were detected in all MAC-BMSCs. MAC-BMSCs had enhanced osteogenesis potential compared with PD-BMSCs. PIK3CA knockdown by shRNA or BYL719 treatment significantly reduced osteogenic differentiation capacity of MAC-BMSCs. RNA-Seq and qRT-PCR revealed the upregulation of distal-less homeobox 5 (DLX5) in MAC-BMSCs compared with PD-BMSCs. The osteogenic potential of MAC-BMSCs was inhibited by DLX5 knockdown, indicating that DLX5 is a downstream target of PIK3CA activation-mediated osteogenesis. This study revealed that osteogenic differentiation in MAC-BMSCs is enhanced by PIK3CA activation mutation through PI3K/AKT/mTOR signaling pathway and can be reversed by PIK3CA knockdown or drug inhibition.
AMG-232 sensitizes high MDM2-expressing tumor cells to T-cell-mediated killing
Authors: Sahin Ilyas , Zhang Shengliang , Navaraj Arunasalam , Zhou Lanlan , Dizon Don , Safran Howard , El-Deiry Wafik S.
Published: July 2020

Oncogenic mouse double minute 2 homolog (MDM2) is an E3-ubiquitin ligase that facilitates proteasomal degradation of p53. MDM2 amplification occurs in cancer and has been implicated in accelerated tumor growth, known as hyper-progression, following immune-checkpoint therapy. MDM2 amplification also predicts poor response to immune-checkpoint inhibitors. We sought to evaluate the role of MDM2 in T-cell-mediated immune resistance. Ovarian clear cell carcinoma cell lines carrying wild-type p53 with low/high MDM2 expression were investigated in a T-cell co-culture system evaluating T-cell-mediated tumor killing. Targeting of MDM2 was achieved by siRNA transfection or a selective MDM2 inhibitor, AMG-232 and tumor cells were tested in the T-cell co-culture system. AMG-232 activated p53 signaling in cancer cells and relative resistance to AMG-232 was observed in high MDM2-expressing cell lines. Cell lines with high MDM2 expression were more resistant to T cell-mediated tumor killing. Targeting MDM2 by gene-silencing or pharmacological blockade with AMG-232 enhanced T-cell killing of cancer cells. AMG-232 potentiated tumor cell killing by T-cells in combination with anti-PD-1 antibody treatment, regardless of changes in PD-L1 expression. The AMG-232 was not toxic to the T-cells. MDM2 inhibition lowered expression of Interleukin-6, a pro-inflammatory pro-tumorigenic cytokine. Our data support targeting MDM2 in tumors with overexpression or amplification of MDM2 as a precision therapy approach to overcome drug resistance including hyper-progression in the context of immune checkpoint therapy.
Self-assembled dodecyl group-modified gelatin microparticle-based hydrogels with angiogenic properties
Authors: Mizuno Yosuke , Taguchi Tetsushi
Published: July 2020

Supplying oxygen and nutrients to implanted cells or tissues is an important factor that improves their survivability and function in regenerative medicine. Various efforts have been made to develop angiogenic materials by incorporating and releasing growth factors such as vascular endothelial growth factor (VEGF). However, these exogenous growth factors have a short half-life under physiological conditions. We therefore designed a novel angiogenic microparticle (C12-MP) comprising Alaska pollock-derived gelatin (ApGltn) modified with a dodecyl group (C12-ApGltn) to stimulate endogenous VEGF secretion. The C12-MP suspension formed an injectable hydrogel, the rheological properties and enzymatic degradation of which were evaluated. RAW264 cells, mouse macrophage-like cells, cultured with C12-MPs, secreted significantly more VEGF than the original ApGltn MPs. Based on laser Doppler perfusion imaging, the C12-MP hydrogel clearly induced increased blood perfusion in a subcutaneous mouse model compared with the original ApGltn microparticle (Org-MP) or phosphate-buffered saline controls. Histological studies revealed that the areas of nuclear factor (NF)-κB, CD31, and myeloperoxidase staining showed a greater increase at the site injected with C12-MPs than at the site injected with the original ApGltn microparticles or phosphate-buffered saline. The C12-MP hydrogel is a promising angiogenic material for constructing vascular beds for cell transplantation by promoting endogenous VEGF secretion without additional growth factors.
Rapid geomagnetic changes inferred from Earth observations and numerical simulations
Authors: Davies Christopher J. , Constable Catherine G.
Published: July 2020

Extreme variations in the direction of Earth’s magnetic field contain important information regarding the operation of the geodynamo. Paleomagnetic studies have reported rapid directional changes reaching 1° yr−1, although the observations are controversial and their relation to physical processes in Earth’s core unknown. Here we show excellent agreement between amplitudes and latitude ranges of extreme directional changes in a suite of geodynamo simulations and a recent observational field model spanning the past 100 kyrs. Remarkably, maximum rates of directional change reach  ~10° yr−1, typically during times of decreasing field strength, almost 100 times faster than current changes. Detailed analysis of the simulations and a simple analogue model indicate that extreme directional changes are associated with movement of reversed flux across the core surface. Our results demonstrate that such rapid variations are compatible with the physics of the dynamo process and suggest that future searches for rapid directional changes should focus on low latitudes.
Publisher Correction: A quantitative sequencing framework for absolute abundance measurements of mucosal and lumenal microbial communities
Authors: Barlow Jacob T. , Bogatyrev Said R. , Ismagilov Rustem F.
Published: July 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Ultrathin-metal-film-based transparent electrodes with relative transmittance surpassing 100%
Authors: Ji Chengang , Liu Dong , Zhang Cheng , Jay Guo L.
Published: July 2020

Flexible transparent electrodes are in significant demand in applications including solar cells, light-emitting diodes, and touch panels. The combination of high optical transparency and high electrical conductivity, however, sets a stringent requirement on electrodes based on metallic materials. To obtain practical sheet resistances, the visible transmittance of the electrodes in previous studies is typically lower than the transparent substrates the electrode structures are built on, namely, the transmittance relative to the substrate is <100%. Here, we demonstrate a flexible dielectric-metal-dielectric-based electrode with ~88.4% absolute transmittance, even higher than the ~88.1% transmittance of the polymer substrate, which results in a relative transmittance of ~100.3%. This non-trivial performance is achieved by leveraging an optimized dielectric-metal-dielectric structure guided by analytical and quantitative principles described in this work, and is attributed to an ultra-thin and ultra-smooth copper-doped silver film with low optical loss and low sheet resistance.
Flow-induced crystallisation of polymers from aqueous solution
Authors: Dunderdale Gary J. , Davidson Sarah J. , Ryan Anthony J. , Mykhaylyk Oleksandr O.
Published: July 2020

Synthetic polymers are thoroughly embedded in the modern society and their consumption grows annually. Efficient routes to their production and processing have never been more important. In this respect, silk protein fibrillation is superior to conventional polymer processing, not only by achieving outstanding physical properties of materials, such as high tensile strength and toughness, but also improved process energy efficiency. Natural silk solidifies in response to flow of the liquid using conformation-dependent intermolecular interactions to desolvate (denature) protein chains. This mechanism is reproduced here by an aqueous poly(ethylene oxide) (PEO) solution, which solidifies at ambient conditions when subjected to flow. The transition requires that an energy threshold is exceeded by the flow conditions, which disrupts a protective hydration shell around polymer molecules, releasing them from a metastable state into the thermodynamically favoured crystalline state. This mechanism requires vastly lower energy inputs and demonstrates an alternative route for polymer processing.
Two-dimensional optomechanical crystal cavity with high quantum cooperativity
Authors: Ren Hengjiang , Matheny Matthew H. , MacCabe Gregory S. , Luo Jie , Pfeifer Hannes , Mirhosseini Mohammad , Painter Oskar
Published: July 2020

Optomechanical systems offer new opportunities in quantum information processing and quantum sensing. Many solid-state quantum devices operate at millikelvin temperatures—however, it has proven challenging to operate nanoscale optomechanical devices at these ultralow temperatures due to their limited thermal conductance and parasitic optical absorption. Here, we present a two-dimensional optomechanical crystal resonator capable of achieving large cooperativity C and small effective bath occupancy nb, resulting in a quantum cooperativity Ceff ≡ C/nb > 1 under continuous-wave optical driving. This is realized using a two-dimensional phononic bandgap structure to host the optomechanical cavity, simultaneously isolating the acoustic mode of interest in the bandgap while allowing heat to be removed by phonon modes outside of the bandgap. This achievement paves the way for a variety of applications requiring quantum-coherent optomechanical interactions, such as transducers capable of bi-directional conversion of quantum states between microwave frequency superconducting quantum circuits and optical photons in a fiber optic network.
Age-dependent hormesis-like effects of the synthetic cannabinoid CP55940 in C57BL/6 mice
Authors: Hodges Erik L. , Marshall Jessica P. , Ashpole Nicole M.
Published: July 2020

Use of cannabis and cannabinoid-containing substances is increasing among geriatric patients, despite relatively sparse preclinical evidence in aged models. To better understand the effects of exogenous cannabinoids on aging male and female rodents, we compared the age- and dose-dependent physiological and behavioral effects of the synthetic cannabinoid CP55940 in young–adult and aged C57BL/6 mice. Locomotion, body temperature, thermal nociception, and fecal output were measured following CP55940 administration. Our findings indicate that CP55940 is more potent and efficacious in older mice, evidenced by exaggerated antinociception and locomotor inhibition when compared to younger adult mice. In addition, we report that low doses of CP55940 paradoxically stimulate locomotion in young–adult (4 m) mice; however, this hormesis-like response is not as evident in aged animals (21–24 m). These bidirectional effects appear to be mediated via the endocannabinoid CB1 and CB2 receptors.
Children’s rare disease cohorts: an integrative research and clinical genomics initiative
Authors: Rockowitz Shira , LeCompte Nicholas , Carmack Mary , Quitadamo Andrew , Wang Lily , Park Meredith , Knight Devon , Sexton Emma , Smith Lacey , Sheidley Beth , Field Michael , Holm Ingrid A. , Brownstein Catherine A. , Agrawal Pankaj B. , Kornetsky Susan , Poduri Annapurna , Snapper Scott B. , Beggs Alan H. , Yu Timothy W. , Williams David A. , Sliz Piotr
Published: July 2020

While genomic data is frequently collected under distinct research protocols and disparate clinical and research regimes, there is a benefit in streamlining sequencing strategies to create harmonized databases, particularly in the area of pediatric rare disease. Research hospitals seeking to implement unified genomics workflows for research and clinical practice face numerous challenges, as they need to address the unique requirements and goals of the distinct environments and many stakeholders, including clinicians, researchers and sequencing providers. Here, we present outcomes of the first phase of the Children’s Rare Disease Cohorts initiative (CRDC) that was completed at Boston Children’s Hospital (BCH). We have developed a broadly sharable database of 2441 exomes from 15 pediatric rare disease cohorts, with major contributions from early onset epilepsy and early onset inflammatory bowel disease. All sequencing data is integrated and combined with phenotypic and research data in a genomics learning system (GLS). Phenotypes were both manually annotated and pulled automatically from patient medical records. Deployment of a genomically-ordered relational database allowed us to provide a modular and robust platform for centralized storage and analysis of research and clinical data, currently totaling 8516 exomes and 112 genomes. The GLS integrates analytical systems, including machine learning algorithms for automated variant classification and prioritization, as well as phenotype extraction via natural language processing (NLP) of clinical notes. This GLS is extensible to additional analytic systems and growing research and clinical collections of genomic and other types of data.
Macroscopic manifestation of domain-wall magnetism and magnetoelectric effect in a Néel-type skyrmion host
Authors: Geirhos Korbinian , Gross Boris , Szigeti Bertalan G. , Mehlin Andrea , Philipp Simon , White Jonathan S. , Cubitt Robert , Widmann Sebastian , Ghara Somnath , Lunkenheimer Peter , Tsurkan Vladimir , Neuber Erik , Ivaneyko Dmytro , Milde Peter , Eng Lukas M. , Leonov Andrey O. , Bordács Sándor , Poggio Martino , Kézsmárki István
Published: July 2020

We report a magnetic state in GaV4Se8 which emerges exclusively in samples with mesoscale polar domains and not in polar mono-domain crystals. It is manifested by a sharp anomaly in the magnetic susceptibility and the magnetic torque, distinct from other anomalies observed also in polar mono-domain samples upon transitions between the cycloidal, the Néel-type skyrmion lattice and the ferromagnetic states. We ascribe this additional transition to the transformation of distinct magnetic textures, confined to polar domain walls (DW), to the ferromagnetic (FM) state. The emergence of these DW-confined magnetic states is likely driven by the mismatch of different spin spirals, hosted by the adjacent domains. A clear anomaly in the magneto-current indicates that the DW-confined magnetic states also have strong contributions to the magnetoelectric response. We expect polar DWs to commonly host such confined magnetic edge states and, thus, offer a fertile ground to explore novel forms of magnetism.
Predicting breast cancer risk using interacting genetic and demographic factors and machine learning
Authors: Behravan Hamid , Hartikainen Jaana M. , Tengström Maria , Kosma Veli–Matti , Mannermaa Arto
Published: July 2020

Breast cancer (BC) is a multifactorial disease and the most common cancer in women worldwide. We describe a machine learning approach to identify a combination of interacting genetic variants (SNPs) and demographic risk factors for BC, especially factors related to both familial history (Group 1) and oestrogen metabolism (Group 2), for predicting BC risk. This approach identifies the best combinations of interacting genetic and demographic risk factors that yield the highest BC risk prediction accuracy. In tests on the Kuopio Breast Cancer Project (KBCP) dataset, our approach achieves a mean average precision (mAP) of 77.78 in predicting BC risk by using interacting genetic and Group 1 features, which is better than the mAPs of 74.19 and 73.65 achieved using only Group 1 features and interacting SNPs, respectively. Similarly, using interacting genetic and Group 2 features yields a mAP of 78.00, which outperforms the system based on only Group 2 features, which has a mAP of 72.57. Furthermore, the gene interaction maps built from genes associated with SNPs that interact with demographic risk factors indicate important BC-related biological entities, such as angiogenesis, apoptosis and oestrogen-related networks. The results also show that demographic risk factors are individually more important than genetic variants in predicting BC risk.
Brain-behaviour correlates of habitual motivation in chronic back pain
Authors: Nees Frauke , Ruttorf Michaela , Fuchs Xaver , Rance Mariela , Beyer Nicole
Published: July 2020

Chronic pain may sap the motivation for positive events and stimuli. This may lead to a negative behavioural cycle reducing the establishment of appetitive habitual engagement. One potential mechanism for this might be biased learning. In our experiment, chronic back pain patients and healthy controls completed an appetitive Pavlovian-instrumental transfer procedure. We examined participants` behaviour and brain activity and reported pain, depression and anxiety. Patients showed reduced habitual behaviour and increased responses in the hippocampus than controls. This behavioural bias was related to motivational value and reflected in the updating of brain activity in prefrontal–striatal–limbic circuits. Moreover, this was influenced by pain symptom duration, depression and anxiety (explained variance: up to 50.7%). Together, findings identify brain-behaviour pathways for maladaptive habitual learning and motivation in chronic back pain, which helps explaining why chronic pain can be resistant to change, and where clinical characteristics are significant modulators.
Bladder cancer-related microbiota: examining differences in urine and tissue samples
Authors: Mansour Bassel , Monyók Ádám , Makra Nóra , Gajdács Márió , Vadnay István , Ligeti Balázs , Juhász János , Szabó Dóra , Ostorházi Eszter
Published: July 2020

The microbiota isolated from the urine of bladder carcinoma patients exhibits significantly increased compositional abundance of some bacterial genera compared to the urine of healthy patients. Our aim was to compare the microbiota composition of cancerous tissues and urine samples collected from the same set of patients in order to improve the accuracy of diagnostic measures. Tissue samples were collected from patients during cancer tissue removal by transurethral resection. In parallel, urine samples were obtained by transurethral resectoscopy from the same patients. The V3–V4 region of the bacterial 16S rRNA gene was sequenced and analyzed using the Kraken pipeline. In the case of four patients, duplicate microbiota analysis from distant parts of the cancerous tissues was highly reproducible, and independent of the site of tissue collection of any given patient. Akkermansia, Bacteroides, Clostridium sensu stricto, Enterobacter and Klebsiella, as “five suspect genera”, were over-represented in tissue samples compared to the urine. To our knowledge, this is the first study comparing urinary and bladder mucosa-associated microbiota profiles in bladder cancer patients. More accurate characterization of changes in microbiota composition during bladder cancer progression could provide new opportunities in the development of appropriate screening or monitoring methods.
Endogenous opioids facilitate intrinsically-rewarded birdsong
Authors: Stevenson Sharon A. , Piepenburg Alice , Spool Jeremy A. , Angyal Caroline S. , Hahn Allison H. , Zhao Changjiu , Riters Lauren V.
Published: July 2020

Many songbirds sing in non-reproductive contexts while in flocks. Singing in such gregarious contexts is critical for maintaining and learning songs; however, song is not directed towards other individuals and has no obvious, immediate social consequences. Studies using conditioned place preference (CPP) tests of reward indicate that song production in gregarious contexts correlates positively with a bird’s intrinsic reward state and with opioid markers in the medial preoptic nucleus (mPOA). However, the causal involvement of opioids in gregarious song is unknown. Here we report that the selective mu opioid receptor (MOR) agonist fentanyl dose-dependently facilitates gregarious song and reduces stress/anxiety-related behavior in male and female European starlings. Furthermore, infusion of siRNA targeting MORs specifically in mPOA both suppresses gregarious song and disrupts the positive association between affective state and singing behavior, as revealed using CPP tests of song-associated reward. Results strongly implicate opioids in gregarious song and suggest that endogenous opioids in the mPOA may facilitate song by influencing an individual’s intrinsic reward state.
Author Correction: Connexin43 expression in bone marrow derived cells contributes to the electrophysiological properties of cardiac scar tissue
Authors: Vasquez Carolina , Mezzano Valeria , Kessler Newman , Swardh Freja , Ernestad Desiree , Mahoney Vanessa M. , Hanna John , Morley Gregory E.
Published: July 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
The unaided recovery of marathon-induced serum metabolome alterations
Authors: Stander Zinandré , Luies Laneke , Mienie Lodewyk J. , Van Reenen Mari , Howatson Glyn , Keane Karen M. , Clifford Tom , Stevenson Emma J. , Loots Du Toit
Published: July 2020

Endurance athlete performance is greatly dependent on sufficient post-race system recovery, as endurance races have substantial physiological, immunological and metabolic effects on these athletes. To date, the effects of numerous recovery modalities have been investigated, however, very limited literature exists pertaining to metabolic recovery of athletes after endurance races without the utilisation of recovery modalities. As such, this investigation is aimed at identifying the metabolic recovery trend of athletes within 48 h after a marathon. Serum samples of 16 athletes collected 24 h before, immediately after, as well as 24 h and 48 h post-marathon were analysed using an untargeted two-dimensional gas chromatography time-of-flight mass spectrometry metabolomics approach. The metabolic profiles of these comparative time-points indicated a metabolic shift from the overall post-marathon perturbed state back to the pre-marathon metabolic state during the recovery period. Statistical analyses of the data identified 61 significantly altered metabolites including amino acids, fatty acids, tricarboxylic acid cycle, carbohydrates and associated intermediates. These intermediates recovered to pre-marathon related concentrations within 24 h post-marathon, except for xylose which only recovered within 48 h. Furthermore, fluctuations in cholesterol and pyrimidine intermediates indicated the activation of alternative recovery mechanisms. Metabolic recovery of the athletes was attained within 48 h post-marathon, most likely due to reduced need for fuel substrate catabolism. This may result in the activation of glycogenesis, uridine-dependent nucleotide synthesis, protein synthesis, and the inactivation of cellular autophagy. These results may be beneficial in identifying more efficient, targeted recovery approaches to improve athletic performance.
Ensuring the spread of referral marketing campaigns: a quantitative treatment
Authors: Ghosh Sayantari , Gaurav Kumar , Bhattacharya Saumik , Singh Yatindra Nath
Published: July 2020

In marketing world, social media is playing a crucial role nowadays. One of the most recent strategies that exploit social contacts for the purpose of marketing, is referral marketing, where a person shares information related to a particular product among his/her social contacts. When this spreading of marketing information goes viral, the diffusion process looks like an epidemic spread. In this work, we perform a systematic study with a goal to device a methodology for using the huge amount of survey data available to understand customer behaviour from a more mathematical and quantitative perspective. We perform an unsupervised natural language processing and hierarchical clustering based analysis of the responses of a recent survey focused on referral marketing to correlate the customers’ psychology with transitional dynamics, and investigate some major determinants that regulate the diffusion of a campaign. In addition to natural language processing for topic modeling, detailed differential equation based analysis and graph theoretical treatment have been carried out to explore the conditions of success for the campaign in terms of realistic parameters both for homogeneous and heterogeneous population structure. Finally, experiments have been performed for generation of a recommendation network to understand the diffusion dynamics in realistic scenario. A complete mathematical treatment with analysis over real social networks helped us to determine key customer motivations and their impacts on a marketing strategy, which are important to ensure an effective spread of a designed marketing campaign. Because of its systematic generalized formulation, the prescribed quantitative framework may be useful in all areas of social dynamics, beyond the field of marketing.