bluuebunny/crossref_metadata_2025 huggingface dataset:
Cue reliability, salience and early comprehension of agreement: Evidence from Greek
Authors: KENANIDIS Panagiotis , CHONDROGIANNI Vicky , LEGENDRE Géraldine , CULBERTSON Jennifer
Published: October 2020

Previous studies across languages (English, Spanish, French) have argued that perceptual salience and cue reliability can explain cross-linguistic differences in early comprehension of verbal agreement. Here we tested this hypothesis further by investigating early comprehension in Greek, where markers have high salience and reliability (compared to Spanish and English) predicting early comprehension, as in French. We investigated two and three-year-old Greek-speaking children's ability to distinguish third person singular and plural agreement in a picture-selection task. We also examined the frequency of these morphemes in child-directed speech to address input effects. Results showed that three-year-olds are sensitive to both singular and plural agreement, earlier than children acquiring English and Spanish, but later than French, and despite singular agreement being more frequent than plural agreement in the child corpus. These findings provide further support for the role of salience and reliability during early acquisition, while highlighting a potential effect of morpheme position.
Between Global Governance and Local Governance: the Shanghai Model of Anti-Covid-19 Epidemic Measures
Authors: Zhudi Ye , Yicheng Yang , Guanhao Sun
Published: October 2020

Given its special geographical location and size, Shanghai is a key hub linking world and locality, in this case China, in the implementation of anti-Covid-19 measures. By coordinating all the work according to the rule of law, Shanghai has outlined the basic framework for fighting the epidemic; by establishing the community grid governance model, Shanghai has soundly harnessed the ‘political potential energy’ and effectively filled in the internal mechanism of anti-Covid-19 and urban governance; and by respecting professionalism and the role of the masses, Shanghai seized the best opportunity to fight against the epidemic. Therefore, Shanghai has built up public value and gained spiritual support to fight against the epidemic and fundamentally improved the governance efficiency of the city. The experience of Shanghai’s anti-epidemic measures and governance forms an organic whole through mutual embedding and ultimately relies on efficient and fair governance.
Is the world converging to a ‘Western diet’?
Authors: Azzam Azzeddine
Published: October 2020

Objective:

To test the nutrition transition hypothesis of global dietary convergence to a ‘Western diet’.

Design:

Consumer-waste-adjusted FAO Food Balance Sheets are used to construct for each country a Western Diet Similarity Index (WSI), expressed as a ratio of calories from animal-sourced foods, oils, fats and sweeteners to total per capita calories. β-Convergence and associated speed are estimated by growth regressions using 1992–2013 panel data. Speed of convergence, a non-linear function of income per capita, globalisation and urbanisation, determines the steady-state or long-term global WSI. The long-term global WSI is compared with the WSI of the group of countries with the highest population-weighted average WSI. The group, determined by K-means cluster analysis, consists of sixteen Western countries.

Setting:

Worldwide.

Participants:

Not applicable.

Results:

Strong evidence of global dietary convergence at a speed driven by income per capita, globalisation and urbanisation with a long-term WSI of 38 %. When compared with the WSI of Western countries (68 %), the hypothesis of global dietary convergence to a Western diet is rejected.

Conclusions:

The nutrition transition is acting in two opposing directions. Some countries experienced positive and others negative WSI growth, slowing down the transition to a Western diet in the long run. Policies to further slowdown the transition by some countries to unhealthier dietary patterns are as important as policies to further speed up the transition by other countries to healthier ones.
Psychometric Properties of the Children’s Version of the Spence Children’s Anxiety Scale (SCAS) in a Spanish Clinical Sample
Authors: Forcadell Eduard , Medrano Laura , Garcia-Delgar Blanca , Fernández-Martínez Iván , Orgilés Mireia , García Carolina , Lázaro Luisa , Lera-Miguel Sara
Published: October 2020

The Spence Children’s Anxiety Scale (SCAS) has demonstrated good psychometric properties in several countries and cultures. Nevertheless, most of the previous studies that explore these properties have combined clinical and community samples. We aimed to validate the Spanish version of the SCAS in a large clinical sample (N = 130) of children and adolescents. The Spanish adaptation of the SCAS showed good internal consistency for the total scale, and good test-retest reliability for all the subscales. Furthermore, its convergent and discriminant validity were supported by significant correlations with other anxiety questionnaires (Screen for Child Anxiety Related Emotional Disorders [SCARED], Youth Self-Report [YSR] subscales for anxiety disorders and internalizing symptomatology), and lower or non-significant correlations with depression symptoms and externalizing symptoms scales respectively. For the first time in a purely clinical sample, the original factor structure of the SCAS based on six correlated factors was confirmed. Future studies need to evaluate whether the factorial structure of the present instrument is the most suitable for use in clinical populations.
Estimation of Physiological Factors Controlling Carbon Isotope Fractionation in Coccolithophores in Photic Zone and Core‐Top Samples
Authors: Hernández‐Almeida Iván , Krumhardt Kristen M. , Zhang Hongrui , Stoll Heather M.
Published: October 2020

Estimates of past pCO2 prior to ice‐core records have often been sought by measuring carbon isotopic fractionation during photosynthesis (Ɛp) in alkenone‐producing algae present in the fossil record. Photic zone and core‐top Ɛp show strong latitudinal gradients, which have been interpreted as an effect of growth rate. The factor b, used in previous studies to account for the changes in growth rate, shows high dependence on [CO2]aq in culture experiments, making difficult the deconvolution of nutrients versus other effects in the field. We combine coccolithophore growth rate output from a global model, limited by sea surface temperature (SST) and [PO43−] with a statistical model that include [CO2]aq, cell size and light to predict Ɛp, and examine the influence of different environmental and physiological variables on the observed expression of Ɛp in field samples. Back calculations of the growth rate necessary to match the observed Ɛp in photic zone and core‐top samples using the statistical model show high correlation with modeled growth rates using [PO43−] and SST in temperate regions. For Southern Ocean and tropical upwelling regions, with colder and warmer SST, respectively, there might be additional factors controlling growth rate not accounted for in the model, such as grazing or nutrient recycling. We evaluate the potential to reconstruct past growth rates using planktonic foraminifera‐ and coccolithophore‐based proxies related to water column structure. We found best application of these proxies as potential indicators of past [PO43−], which can subsequently be used in combination with proxy temperature, to estimate past coccolithophore growth rates.
P/Ca in Carbonates as a Proxy for Alkalinity and Phosphate Levels
Authors: Ingalls Miquela , Blättler Clara L. , Higgins John A. , Magyar John S. , Eiler John M. , Fischer Woodward W.
Published: October 2020

Understanding mechanisms, rates, and drivers of past carbonate formation provides insight into the chemical evolution of Earth's oceans and atmosphere. We paired geological observations with elemental and isotope geochemistry to test potential proxies for calcium‐to‐alkalinity ratios (Ca:ALK). Across diverse carbonate facies from Pleistocene closed‐basin lakes in Owens Valley, CA, we observed less δ44/40Ca variation than theoretically predicted (>0.75‰) for the very low Ca:ALK in these systems. Carbonate clumped isotope disequilibria implied rapid carbonate growth—kinetic isotope effects, combined with the diverse carbonate minerals present, complicated the interpretation of δ44/40Ca as a paleoalkalinity proxy. In contrast, we observed that the high phosphate concentrations are recorded by shoreline and lake bottom carbonates formed in 11 Pleistocene lakes at orders of magnitude greater concentrations than in marine carbonates. Because the maximum phosphate content of water depends on Ca:ALK, we propose that carbonate P/Ca can inform phosphate levels and thereby Ca:ALK of aqueous environments in the carbonate record.
Application of Constitutive Friction Laws to Glacier Seismicity
Authors: Zoet L. K. , Ikari M. J. , Alley R. B. , Marone C. , Anandakrishnan S. , Carpenter B. M. , Scuderi M. M.
Published: October 2020

While analysis of glacial seismicity continues to be a widely used method for interpreting glacial processes, the underlying mechanics controlling glacial stick‐slip seismicity remain speculative. Here, we report on laboratory shear experiments of debris‐laden ice slid over a bedrock asperity under carefully controlled conditions. By modifying the elastic loading stiffness, we generated the first laboratory icequakes. Our work represents the first comprehensive lab observations of unstable ice‐slip events and replicates several seismological field observations of glacier slip, such as slip velocity, stress drop, and the relationship between stress drop and recurrence interval. We also observe that stick‐slips initiate above a critical driving velocity and that stress drop magnitude decreases with further increases in velocity, consistent with friction theory and rock‐on‐rock friction laboratory experiments. Our results demonstrate that glacier slip behavior can be accurately predicted by the constitutive rate‐and‐state friction laws that were developed for rock friction.
Breaking the Ice: Identifying Hydraulically Forced Crevassing
Authors: Hudson T. S. , Brisbourne A. M. , White R. S. , Kendall J. M. , Arthern R. , Smith A. M.
Published: October 2020

Hydraulically forced crevassing is thought to reduce the stability of ice shelves and ice sheets, affecting structural integrity and providing pathways for surface meltwater to the bed. It can cause ice shelves to collapse and ice sheets to accelerate into the ocean. However, direct observations of the hydraulically forced crevassing process remain elusive. Here we report a novel method and observations that use icequakes to directly observe crevassing and determine the role of hydrofracture. Crevasse icequake depths from seismic observations are compared to a theoretically derived maximum dry crevasse depth. We observe icequakes below this depth, suggesting hydrofracture. Furthermore, icequake source mechanisms provide insight into the fracture process, with predominantly opening cracks observed, which have opening volumes of hundredths of a cubic meter. Our method and findings provide a framework for studying a critical process that is key for the stability of ice shelves and ice sheets and, therefore, future sea level rise projections.
Formyl peptide receptors in the mucosal immune system
Authors: Jeong Yu Sun , Bae Yoe-Sik
Published: October 2020

Formyl peptide receptors (FPRs) belong to the G protein-coupled receptor (GPCR) family and are well known as chemotactic receptors and pattern recognition receptors (PRRs) that recognize bacterial and mitochondria-derived formylated peptides. FPRs are also known to detect a wide range of ligands, including host-derived peptides and lipids. FPRs are highly expressed not only in phagocytes such as neutrophils, monocytes, and macrophages but also in nonhematopoietic cells such as epithelial cells and endothelial cells. Mucosal surfaces, including the gastrointestinal tract, the respiratory tract, the oral cavity, the eye, and the reproductive tract, separate the external environment from the host system. In mucosal surfaces, the interaction between the microbiota and host cells needs to be strictly regulated to maintain homeostasis. By sharing the same FPRs, immune cells and epithelial cells may coordinate pathophysiological responses to various stimuli, including microbial molecules derived from the normal flora. Accumulating evidence shows that FPRs play important roles in maintaining mucosal homeostasis. In this review, we summarize the roles of FPRs at mucosal surfaces.
Inhibiting insulin and mTOR signaling by afatinib and crizotinib combination fosters broad cytotoxic effects in cutaneous malignant melanoma
Authors: Das Ishani , Chen Huiqin , Maddalo Gianluca , Tuominen Rainer , Rebecca Vito W. , Herlyn Meenhard , Hansson Johan , Davies Michael A. , Egyházi Brage Suzanne
Published: October 2020

Current treatment modalities for disseminated cutaneous malignant melanoma (CMM) improve survival, however disease progression commonly ensues. In a previous study we identified afatinib and crizotinib in combination as a novel potential therapy for CMM independent of BRAF/NRAS mutation status. Herein, we elucidate the underlying mechanisms of the combination treatment effect to find biomarkers and novel targets for development of therapy that may provide clinical benefit by proteomic analysis of CMM cell lines and xenografts using mass spectrometry based analysis and reverse phase protein array. Identified candidates were validated using immunoblotting or immunofluorescence. Our analysis revealed that mTOR/Insulin signaling pathways were significantly decreased by the afatinib and crizotinib combination treatment. Both in vitro and in vivo analyses showed that the combination treatment downregulated pRPS6KB1 and pRPS6, downstream of mTOR signaling, and IRS-1 in the insulin signaling pathway, specifically ablating IRS-1 nuclear signal. Silencing of RPS6 and IRS-1 alone had a similar effect on cell death, which was further induced when IRS-1 and RPS6 were concomitantly silenced in the CMM cell lines. Silencing of IRS-1 and RPS6 resulted in reduced sensitivity towards combination treatment. Additionally, we found that IRS-1 and RPS6KB1 expression levels were increased in advanced stages of CMM clinical samples. We could demonstrate that induced resistance towards combination treatment was reversible by a drug holiday. CD171/L1CAM, mTOR and PI3K-p85 were induced in the combination resistant cells whereas AXL and EPHA2, previously identified mediators of resistance to MAPK inhibitor therapy in CMM were downregulated. We also found that CD171/L1CAM and mTOR were increased at progression in tumor biopsies from two matched cases of patients receiving targeted therapy with BRAFi. Overall, these findings provide insights into the molecular mechanisms behind the afatinib and crizotinib combination treatment effect and leverages a platform for discovering novel biomarkers and therapy regimes for CMM treatment.
Downregulation of PUMA underlies resistance to FGFR1 inhibitors in the stem cell leukemia/lymphoma syndrome
Authors: Liu Yun , Cai Baohuan , Chong Yating , Zhang Hualei , Kemp Chesley-Anne , Lu Sumin , Chang Chang-Sheng , Ren Mingqiang , Cowell John K. , Hu Tianxiang
Published: October 2020

Resistance to molecular therapies frequently occur due to genetic changes affecting the targeted pathway. In myeloid and lymphoid leukemias/lymphomas resulting from constitutive activation of FGFR1 kinases, resistance has been shown to be due either to mutations in FGFR1 or deletions of PTEN. RNA-Seq analysis of the resistant clones demonstrates expression changes in cell death pathways centering on the p53 upregulated modulator of apoptosis (Puma) protein. Treatment with different tyrosine kinase inhibitors (TKIs) revealed that, in both FGFR1 mutation and Pten deletion-mediated resistance, sustained Akt activation in resistant cells leads to compromised Puma activation, resulting in suppression of TKI-induced apoptosis. This suppression of Puma is achieved as a result of sequestration of inactivated p-Foxo3a in the cytoplasm. CRISPR/Cas9 mediated knockout of Puma in leukemic cells led to an increased drug resistance in the knockout cells demonstrating a direct role in TKI resistance. Since Puma promotes cell death by targeting Bcl2, TKI-resistant cells showed high Bcl2 levels and targeting Bcl2 with Venetoclax (ABT199) led to increased apoptosis in these cells. In vivo treatment of mice xenografted with resistant cells using ABT199 suppressed leukemogenesis and led to prolonged survival. This in-depth survey of the underlying genetic mechanisms of resistance has identified a potential means of treating FGFR1-driven malignancies that are resistant to FGFR1 inhibitors.
MEKK3-MEK5-ERK5 signaling promotes mitochondrial degradation
Authors: Craig Jane E. , Miller Joseph N. , Rayavarapu Raju R. , Hong Zhenya , Bulut Gamze B. , Zhuang Wei , Sakurada Sadie Miki , Temirov Jamshid , Low Jonathan A. , Chen Taosheng , Pruett-Miller Shondra M. , Huang Lily Jun-shen , Potts Malia B.
Published: October 2020

Mitochondria are vital organelles that coordinate cellular energy homeostasis and have important roles in cell death. Therefore, the removal of damaged or excessive mitochondria is critical for maintaining proper cellular function. The PINK1-Parkin pathway removes acutely damaged mitochondria through a well-characterized mitophagy pathway, but basal mitochondrial turnover occurs via distinct and less well-understood mechanisms. Here we report that the MEKK3-MEK5-ERK5 kinase cascade is required for mitochondrial degradation in the absence of exogenous damage. We demonstrate that genetic or pharmacological inhibition of the MEKK3-MEK5-ERK5 pathway increases mitochondrial content by reducing lysosome-mediated degradation of mitochondria under basal conditions. We show that the MEKK3-MEK5-ERK5 pathway plays a selective role in basal mitochondrial degradation but is not required for non-selective bulk autophagy, damage-induced mitophagy, or restraint of mitochondrial biogenesis. This illuminates the MEKK3-MEK5-ERK5 pathway as a positive regulator of mitochondrial degradation that acts independently of exogenous mitochondrial stressors.
Contribution of GATA6 to homeostasis of the human upper pilosebaceous unit and acne pathogenesis
Authors: Oulès Bénédicte , Philippeos Christina , Segal Joe , Tihy Matthieu , Vietri Rudan Matteo , Cujba Ana-Maria , Grange Philippe A. , Quist Sven , Natsuga Ken , Deschamps Lydia , Dupin Nicolas , Donati Giacomo , Watt Fiona M.
Published: October 2020

Although acne is the most common human inflammatory skin disease, its pathogenic mechanisms remain incompletely understood. Here we show that GATA6, which is expressed in the upper pilosebaceous unit of normal human skin, is down-regulated in acne. GATA6 controls keratinocyte proliferation and differentiation to prevent hyperkeratinisation of the infundibulum, which is the primary pathological event in acne. When overexpressed in immortalised human sebocytes, GATA6 triggers a junctional zone and sebaceous differentiation program whilst limiting lipid production and cell proliferation. It modulates the immunological repertoire of sebocytes, notably by upregulating PD-L1 and IL10. GATA6 expression contributes to the therapeutic effect of retinoic acid, the main treatment for acne. In a human sebaceous organoid model GATA6-mediated down-regulation of the infundibular differentiation program is mediated by induction of TGFβ signalling. We conclude that GATA6 is involved in regulation of the upper pilosebaceous unit and may be an actionable target in the treatment of acne.
Selective neuronal degeneration in MATR3 S85C knock-in mouse model of early-stage ALS
Authors: Kao Ching Serena , van Bruggen Rebekah , Kim Jihye Rachel , Chen Xiao Xiao Lily , Chan Cadia , Lee Jooyun , Cho Woo In , Zhao Melody , Arndt Claudia , Maksimovic Katarina , Khan Mashiat , Tan Qiumin , Wilson Michael D. , Park Jeehye
Published: October 2020

A missense mutation, S85C, in the MATR3 gene is a genetic cause for amyotrophic lateral sclerosis (ALS). It is unclear how the S85C mutation affects MATR3 function and contributes to disease. Here, we develop a mouse model that harbors the S85C mutation in the endogenous Matr3 locus using the CRISPR/Cas9 system. MATR3 S85C knock-in mice recapitulate behavioral and neuropathological features of early-stage ALS including motor impairment, muscle atrophy, neuromuscular junction defects, Purkinje cell degeneration and neuroinflammation in the cerebellum and spinal cord. Our neuropathology data reveals a loss of MATR3 S85C protein in the cell bodies of Purkinje cells and motor neurons, suggesting that a decrease in functional MATR3 levels or loss of MATR3 function contributes to neuronal defects. Our findings demonstrate that the MATR3 S85C mouse model mimics aspects of early-stage ALS and would be a promising tool for future basic and preclinical research.
Altered G1 signaling order and commitment point in cells proliferating without CDK4/6 activity
Authors: Liu Chad , Konagaya Yumi , Chung Mingyu , Daigh Leighton H. , Fan Yilin , Yang Hee Won , Terai Kenta , Matsuda Michiyuki , Meyer Tobias
Published: October 2020

Cell-cycle entry relies on an orderly progression of signaling events. To start, cells first activate the kinase cyclin D-CDK4/6, which leads to eventual inactivation of the retinoblastoma protein Rb. Hours later, cells inactivate APC/CCDH1 and cross the final commitment point. However, many cells with genetically deleted cyclin Ds, which activate and confer specificity to CDK4/6, can compensate and proliferate. Despite its importance in cancer, how this entry mechanism operates remains poorly characterized, and whether cells use this path under normal conditions remains unknown. Here, using single-cell microscopy, we demonstrate that cells with acutely inhibited CDK4/6 enter the cell cycle with a slowed and fluctuating cyclin E-CDK2 activity increase. Surprisingly, with low CDK4/6 activity, the order of APC/CCDH1 and Rb inactivation is reversed in both cell lines and wild-type mice. Finally, we show that as a consequence of this signaling inversion, Rb inactivation replaces APC/CCDH1 inactivation as the point of no return. Together, we elucidate the molecular steps that enable cell-cycle entry without CDK4/6 activity. Our findings not only have implications in cancer resistance, but also reveal temporal plasticity underlying the G1 regulatory circuit.
CHIP phosphorylation by protein kinase G enhances protein quality control and attenuates cardiac ischemic injury
Authors: Ranek Mark J. , Oeing Christian , Sanchez-Hodge Rebekah , Kokkonen-Simon Kristen M. , Dillard Danielle , Aslam M. Imran , Rainer Peter P. , Mishra Sumita , Dunkerly-Eyring Brittany , Holewinski Ronald J. , Virus Cornelia , Zhang Huaqun , Mannion Matthew M. , Agrawal Vineet , Hahn Virginia , Lee Dong I. , Sasaki Masayuki , Van Eyk Jennifer E. , Willis Monte S. , Page Richard C. , Schisler Jonathan C. , Kass David A.
Published: October 2020

Proteotoxicity from insufficient clearance of misfolded/damaged proteins underlies many diseases. Carboxyl terminus of Hsc70-interacting protein (CHIP) is an important regulator of proteostasis in many cells, having E3-ligase and chaperone functions and often directing damaged proteins towards proteasome recycling. While enhancing CHIP functionality has broad therapeutic potential, prior efforts have all relied on genetic upregulation. Here we report that CHIP-mediated protein turnover is markedly post-translationally enhanced by direct protein kinase G (PKG) phosphorylation at S20 (mouse, S19 human). This increases CHIP binding affinity to Hsc70, CHIP protein half-life, and consequent clearance of stress-induced ubiquitinated-insoluble proteins. PKG-mediated CHIP-pS20 or expressing CHIP-S20E (phosphomimetic) reduces ischemic proteo- and cytotoxicity, whereas a phospho-silenced CHIP-S20A amplifies both. In vivo, depressing PKG activity lowers CHIP-S20 phosphorylation and protein, exacerbating proteotoxicity and heart dysfunction after ischemic injury. CHIP-S20E knock-in mice better clear ubiquitinated proteins and are cardio-protected. PKG activation provides post-translational enhancement of protein quality control via CHIP.
Large array of Schrödinger cat states facilitated by an optical waveguide
Authors: Leong Wui Seng , Xin Mingjie , Chen Zilong , Chai Shijie , Wang Yu , Lan Shau-Yu
Published: October 2020

Quantum engineering using photonic structures offer new capabilities for atom-photon interactions for quantum optics and atomic physics, which could eventually lead to integrated quantum devices. Despite the rapid progress in the variety of structures, coherent excitation of the motional states of atoms in a photonic waveguide using guided modes has yet to be demonstrated. Here, we use the waveguide mode of a hollow-core photonic crystal fibre to manipulate the mechanical Fock states of single atoms in a harmonic potential inside the fibre. We create a large array of Schrödinger cat states, a quintessential feature of quantum physics and a key element in quantum information processing and metrology, of approximately 15000 atoms along the fibre by entangling the electronic state with the coherent harmonic oscillator state of each individual atom. Our results provide a useful step for quantum information and simulation with a wide range of photonic waveguide systems.
Siah2 integrates mitogenic and extracellular matrix signals linking neuronal progenitor ciliogenesis with germinal zone occupancy
Authors: Ong Taren , Trivedi Niraj , Wakefield Randall , Frase Sharon , Solecki David J.
Published: October 2020

Evidence is lacking as to how developing neurons integrate mitogenic signals with microenvironment cues to control proliferation and differentiation. We determine that the Siah2 E3 ubiquitin ligase functions in a coincidence detection circuit linking responses to the Shh mitogen and the extracellular matrix to control cerebellar granule neurons (CGN) GZ occupancy. We show that Shh signaling maintains Siah2 expression in CGN progenitors (GNPs) in a Ras/Mapk-dependent manner. Siah2 supports ciliogenesis in a feed-forward fashion by restraining cilium disassembly. Efforts to identify sources of the Ras/Mapk signaling led us to discover that GNPs respond to laminin, but not vitronectin, in the GZ microenvironment via integrin β1 receptors, which engages the Ras/Mapk cascade with Shh, and that this niche interaction is essential for promoting GNP ciliogenesis. As GNPs leave the GZ, differentiation is driven by changing extracellular cues that diminish Siah2-activity leading to primary cilia shortening and attenuation of the mitogenic response.
Birefringent Fourier filtering for single molecule coordinate and height super-resolution imaging with dithering and orientation
Authors: Curcio Valentina , Alemán-Castañeda Luis A. , Brown Thomas G. , Brasselet Sophie , Alonso Miguel A.
Published: October 2020

Super-resolution imaging based on single molecule localization allows accessing nanometric-scale information in biological samples with high precision. However, complete measurements including molecule orientation are still challenging. Orientation is intrinsically coupled to position in microscopy imaging, and molecular wobbling during the image integration time can bias orientation measurements. Providing 3D molecular orientation and orientational fluctuations would offer new ways to assess the degree of alignment of protein structures, which cannot be monitored by pure localization. Here we demonstrate that by adding polarization control to phase control in the Fourier plane of the imaging path, all parameters can be determined unambiguously from single molecules: 3D spatial position, 3D orientation and wobbling or dithering angle. The method, applied to fluorescent labels attached to single actin filaments, provides precisions within tens of nanometers in position and few degrees in orientation.
A three-dimensional thalamocortical dataset for characterizing brain heterogeneity
Authors: Prasad Judy A. , Balwani Aishwarya H. , Johnson Erik C. , Miano Joseph D. , Sampathkumar Vandana , De Andrade Vincent , Fezzaa Kamel , Du Ming , Vescovi Rafael , Jacobsen Chris , Kording Konrad P. , Gürsoy Doga , Gray Roncal William , Kasthuri Narayanan , Dyer Eva L.
Published: October 2020

Neural microarchitecture is heterogeneous, varying both across and within brain regions. The consistent identification of regions of interest is one of the most critical aspects in examining neurocircuitry, as these structures serve as the vital landmarks with which to map brain pathways. Access to continuous, three-dimensional volumes that span multiple brain areas not only provides richer context for identifying such landmarks, but also enables a deeper probing of the microstructures within. Here, we describe a three-dimensional X-ray microtomography imaging dataset of a well-known and validated thalamocortical sample, encompassing a range of cortical and subcortical structures from the mouse brain . In doing so, we provide the field with access to a micron-scale anatomical imaging dataset ideal for studying heterogeneity of neural structure.
A contemporary baseline record of the world’s coral reefs
Authors: Rodriguez-Ramirez Alberto , González-Rivero Manuel , Beijbom Oscar , Bailhache Christophe , Bongaerts Pim , Brown Kristen T. , Bryant Dominic E. P. , Dalton Peter , Dove Sophie , Ganase Anjani , Kennedy Emma V. , Kim Catherine J. S. , Lopez-Marcano Sebastian , Neal Benjamin P. , Radice Veronica Z. , Vercelloni Julie , Beyer Hawthorne L. , Hoegh-Guldberg Ove
Published: October 2020

Addressing the global decline of coral reefs requires effective actions from managers, policymakers and society as a whole. Coral reef scientists are therefore challenged with the task of providing prompt and relevant inputs for science-based decision-making. Here, we provide a baseline dataset, covering 1300 km of tropical coral reef habitats globally, and comprised of over one million geo-referenced, high-resolution photo-quadrats analysed using artificial intelligence to automatically estimate the proportional cover of benthic components. The dataset contains information on five major reef regions, and spans 2012–2018, including surveys before and after the 2016 global bleaching event. The taxonomic resolution attained by image analysis, as well as the spatially explicit nature of the images, allow for multi-scale spatial analyses, temporal assessments (decline and recovery), and serve for supporting image recognition developments. This standardised dataset across broad geographies offers a significant contribution towards a sound baseline for advancing our understanding of coral reef ecology and thereby taking collective and informed actions to mitigate catastrophic losses in coral reefs worldwide.
Machine learning-based prediction of microsatellite instability and high tumor mutation burden from contrast-enhanced computed tomography in endometrial cancers
Authors: Veeraraghavan Harini , Friedman Claire F. , DeLair Deborah F. , Ninčević Josip , Himoto Yuki , Bruni Silvio G. , Cappello Giovanni , Petkovska Iva , Nougaret Stephanie , Nikolovski Ines , Zehir Ahmet , Abu-Rustum Nadeem R. , Aghajanian Carol , Zamarin Dmitriy , Cadoo Karen A. , Diaz Luis A. , Leitao Mario M. , Makker Vicky , Soslow Robert A. , Mueller Jennifer J. , Weigelt Britta , Lakhman Yulia
Published: October 2020

To evaluate whether radiomic features from contrast-enhanced computed tomography (CE-CT) can identify DNA mismatch repair deficient (MMR-D) and/or tumor mutational burden-high (TMB-H) endometrial cancers (ECs). Patients who underwent targeted massively parallel sequencing of primary ECs between 2014 and 2018 and preoperative CE-CT were included (n = 150). Molecular subtypes of EC were assigned using DNA polymerase epsilon (POLE) hotspot mutations and immunohistochemistry-based p53 and MMR protein expression. TMB was derived from sequencing, with > 15.5 mutations-per-megabase as a cut-point to define TMB-H tumors. After radiomic feature extraction and selection, radiomic features and clinical variables were processed with the recursive feature elimination random forest classifier. Classification models constructed using the training dataset (n = 105) were then validated on the holdout test dataset (n = 45). Integrated radiomic-clinical classification distinguished MMR-D from copy number (CN)-low-like and CN-high-like ECs with an area under the receiver operating characteristic curve (AUROC) of 0.78 (95% CI 0.58–0.91). The model further differentiated TMB-H from TMB-low (TMB-L) tumors with an AUROC of 0.87 (95% CI 0.73–0.95). Peritumoral-rim radiomic features were most relevant to both classifications (p ≤ 0.044). Radiomic analysis achieved moderate accuracy in identifying MMR-D and TMB-H ECs directly from CE-CT. Radiomics may provide an adjunct tool to molecular profiling, especially given its potential advantage in the setting of intratumor heterogeneity.
MicroRNA dynamics during hibernation of the Australian central bearded dragon (Pogona vitticeps)
Authors: Capraro Alexander , O‘Meally Denis , Waters Shafagh A. , Patel Hardip R. , Georges Arthur , Waters Paul D.
Published: October 2020

Hibernation is a physiological state employed by many animals that are exposed to limited food and adverse winter conditions. Controlling tissue-specific and organism wide changes in metabolism and cellular function requires precise regulation of gene expression, including by microRNAs (miRNAs). Here we profile miRNA expression in the central bearded dragon (Pogona vitticeps) using small RNA sequencing of brain, heart, and skeletal muscle from individuals in late hibernation and four days post-arousal. A total of 1295 miRNAs were identified in the central bearded dragon genome; 664 of which were novel to central bearded dragon. We identified differentially expressed miRNAs (DEmiRs) in all tissues and correlated mRNA expression with known and predicted target mRNAs. Functional analysis of DEmiR targets revealed an enrichment of differentially expressed mRNA targets involved in metabolic processes. However, we failed to reveal biologically relevant tissue-specific processes subjected to miRNA-mediated regulation in heart and skeletal muscle. In brain, neuroprotective pathways were identified as potential targets regulated by miRNAs. Our data suggests that miRNAs are necessary for modulating the shift in cellular metabolism during hibernation and regulating neuroprotection in the brain. This study is the first of its kind in a hibernating reptile and provides key insight into this ephemeral phenotype.
A possible link between coral reef success, crustose coralline algae and the evolution of herbivory
Authors: Teichert Sebastian , Steinbauer Manuel , Kiessling Wolfgang
Published: October 2020

Crustose coralline red algae (CCA) play a key role in the consolidation of many modern tropical coral reefs. It is unclear, however, if their function as reef consolidators was equally pronounced in the geological past. Using a comprehensive database on ancient reefs, we show a strong correlation between the presence of CCA and the formation of true coral reefs throughout the last 150 Ma. We investigated if repeated breakdowns in the potential capacity of CCA to spur reef development were associated with sea level, ocean temperature, CO2concentration, CCA species diversity, and/or the evolution of major herbivore groups. Model results show that the correlation between the occurrence of CCA and the development of true coral reefs increased with CCA diversity and cooler ocean temperatures while the diversification of herbivores had a transient negative effect. The evolution of novel herbivore groups compromised the interaction between CCA and true reef growth at least three times in the investigated time interval. These crises have been overcome by morphological adaptations of CCA.
Association between serum CCL-18 and IL-23 concentrations and disease progression of chronic obstructive pulmonary disease
Authors: Rong Biaoxue , Fu Tian , Rong Congxue , Liu Wen , Li Kai , Liu Hua
Published: October 2020

This study aimed to investigate the association between serum concentrations of chemokine (C–C Motif) ligand 18 (CCL-18) and interleukin 23 (IL-23) and clinical parameters of chronic obstructive pulmonary disease (COPD). The serum concentrations of CCL-18 and IL-23 were tested by enzyme linked immunosorbent assay (ELISA). The association between their concentrations and clinical parameters of COPD patients were analyzed by linear regression, logistic regression and ROC curve. The results showed that the serum concentrations of CCL-18 and IL-23 in COPD patients were increased compared with healthy people (P < 0.001) and that patients with acute exacerbation of COPD (AECOPD) had higher serum CCL-18 and IL-23 concentrations than stable patients (P < 0.001). Synergistic increase of CCL-18 and IL-23 in COPD patients was positively correlated with COPD patients' higher GOLD grade (P < 0.001), higher mMRC score (P < 0.001) and longer medical history (P < 0.001), but negatively correlated with the forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) (P < 0.001) and FEV1% predicted (P < 0.001). The serum concentrations of CCL-18 and IL-23 were most related to the GOLD grade (OR = 2.764 for CCL-18 and OR = 4.215 for IL-23) and detection of both showed considerable sensitivity (72.57% for CCL-18 and 76.92% for IL-23) and specificity (92.50% for CCL-18 and 77.5% for IL-23) in identifying COPD. Increased serum concentrations of CCL-18 and IL-23 correlated with the disease progression of COPD and they could be used as biomarkers for disease evaluation of COPD.
Deletion of CD38 and supplementation of NAD+ attenuate axon degeneration in a mouse facial nerve axotomy model
Authors: Takaso Yuji , Noda Masao , Hattori Tsuyoshi , Roboon Jureepon , Hatano Miyako , Sugimoto Hisashi , Brenner Charles , Yamamoto Yasuhiko , Okamoto Hiroshi , Higashida Haruhiro , Ito Makoto , Yoshizaki Tomokazu , Hori Osamu
Published: October 2020

Following facial nerve axotomy, nerve function is not fully restored even after reconstruction. This may be attributed to axon degeneration/neuronal death and sustained neuroinflammation. CD38 is an enzyme that catalyses the hydrolysis of nicotinamide adenine dinucleotide (NAD+) and is a candidate molecule for regulating neurodegeneration and neuroinflammation. In this study, we analyzed the effect of CD38 deletion and NAD+supplementation on neuronal death and glial activation in the facial nucleus in the brain stem, and on axon degeneration and immune cell infiltration in the distal portion of the facial nerve after axotomy in mice. Compared with wild-type mice, CD38 knockout (KO) mice showed reduced microglial activation in the facial nucleus, whereas the levels of neuronal death were not significantly different. In contrast, the axon degeneration and demyelination were delayed, and macrophage accumulation was reduced in the facial nerve of CD38 KO mice after axotomy. Supplementation of NAD+with nicotinamide riboside slowed the axon degeneration and demyelination, although it did not alter the level of macrophage infiltration after axotomy. These results suggest that CD38 deletion and supplementation of NAD+may protect transected axon cell-autonomously after facial nerve axotomy.
Occurrence of multiclass endocrine disrupting compounds in a drinking water supply system and associated risks
Authors: Wee Sze Yee , Aris Ahmad Zaharin , Yusoff Fatimah Md. , Praveena Sarva Mangala
Published: October 2020

Contamination by endocrine disrupting compounds (EDCs) concerns the security and sustainability of a drinking water supply system and human exposure via water consumption. This study analyzed the selected EDCs in source (river water, n = 10) and supply (tap water, n = 155) points and the associated risks. A total of 14 multiclass EDCs was detected in the drinking water supply system in Malaysia. Triclosan (an antimicrobial agent) and 4-octylphenol (a plasticizer) were only detected in the tap water (up to 9.74 and 0.44 ng/L, respectively). Meanwhile, chloramphenicol and 4-nonylphenol in the system were below the method detection limits. Bisphenol A was observed to be highest in tap water at 66.40 ng/L (detection: 100%; median concentration: 0.28 ng/L). There was a significant difference in triclosan contamination between the river and tap water (p < 0.001). Overall, the life groups were estimated at no possible risk of EDCs (risk quotient < 1). Nonetheless, the results concern the transport and impact of EDCs on the drinking water supply system regarding treatment sustainability and water security. Further exploration of smart monitoring and management using Big Data and Internet of Things and the need to invent rapid, robust, sensitive, and efficient sensors is warranted.
The relationship between axial length, age and intraocular pressure in children with primary congenital glaucoma
Authors: Al-Obaida Ibrahim , Al Owaifeer Adi Mohammed , Ahmad Khabir , Malik Rizwan
Published: October 2020

Whilst axial length (AxL) from ultrasound examination is a useful clinical parameter for monitoring progression in younger children with glaucoma, distinguishing AxL changes due to raised intraocular pressure (IOP) from age is often challenging. Existing normograms have included a limited number of children with glaucoma. The aim of this study was to evaluate the relationship between AxL with age and IOP in children with primary congenital glaucoma (PCG) and develop a model for expected AxL increase with age. All children (n = 208; 397 eyes) with PCG who attended our tertiary eye care facility from June 2014 and July 2018 and had AxL and IOP measurements were included. The relationship of AxL with age and IOP was studied by applying a LOWESS fit and then mixed effects models. In the final model, age was the most significant factor influencing the growth of AxL (coefficient age 3.14[95% CI 2.91–3.35, p < 0.001], coefficient age2 − 0.53[95% CI, − 0.59 to − 0.47, p < 0.001]), and this association was influenced by the interaction of IOP with sex (p = 0.098 for girls relative to boys), the number of antiglaucoma medications (AGM [p < 0.001 for ≥ 3 AGM]) and glaucoma surgery (p = 0.015). This model enabled us to derive predicted values for clinical use in children with PCG to predict those with progressive glaucoma.
Prevalence of Malassezia species on the skin of HIV-seropositive patients
Authors: Krzyściak Paweł , Bakuła Zofia , Gniadek Agnieszka , Garlicki Aleksander , Tarnowski Mikołaj , Wichowski Michał , Jagielski Tomasz
Published: October 2020

Malassezia is a genus of lipophilic yeasts residing on the skin of warm-blooded animals. The correlation between specific species and their involvement in skin diseases has been well researched. However, only very few studies have investigated the distribution of Malassezia spp. on the healthy skin of patients infected with human immunodeficiency virus (HIV). The purpose of this work was to analyze whether the composition of Malassezia spp. isolated from the skin of the HIV-infected patients differs from that of healthy individuals. The study included a total of 96 subjects, who were divided into two equally sized groups: HIV-seropositive and HIV-seronegative. The specimens were collected from the subjects by swabbing four anatomical sites (face, chest, back, and scalp). Species were identified using phenotype-based methods, and the identification of strains isolated from the HIV-seropositive patients was confirmed by PCR sequencing of the rDNA cluster. Malassezia spp. were isolated from 33 (69%) HIV-seropositive patients and 38 (79%) healthy volunteers. It was found that men were much more likely to have their heads colonized with Malassezia spp. than women. The most prevalent species on the skin of both HIV-seropositive and HIV-seronegative individuals were Malassezia sympodialis, M. globosa, and M. furfur, albeit at different proportions in the two populations. The diversity of Malassezia spp. was the highest on the face of the HIV-seropositive patients (Shannon–Weiner Index H = 1.35) and lowest on the back of the healthy volunteers (H = 0.16). The phenotype- and molecular-based identification methods were congruent at 94.9%. It was observed a tendency that the HIV-seropositive patients had higher CD4+ cell counts, indicating higher colonization with Malassezia spp.
Validation of galectin-1 as potential diagnostic biomarker of early rheumatoid arthritis
Authors: Triguero-Martínez Ana , de la Fuente Hortensia , Montes Nuria , Ortiz Ana María , Roy-Vallejo Emilia , Castañeda Santos , González-Alvaro Isidoro , Lamana Amalia
Published: October 2020

Galectin 1 (Gal1) is a lectin with a wide cellular expression that functions as a negative regulator of the immune system in several animal models of autoimmune diseases. Identification of patients with rheumatoid arthritis (RA) has improved during the last decade, although there is still a need for biomarkers allowing an early diagnosis. In this regard, it has been recently proposed that Gal1 serum levels are increased in patients with RA compared to the general population. However, this topic is controversial in the literature. In this work, we provide additional information about the potential usefulness of Gal1 serum levels as a biomarker for RA diagnosis. We studied Gal1 serum and synovial fluid levels and clinical parameters in samples from 62 patients with early arthritis belonging to the PEARL study. In addition, 24 healthy donors were studied. We found that both patients fulfilling RA criteria and patients with undifferentiated arthritis showed higher Gal1 levels than healthy donors. Similar findings were observed in synovial fluid, which showed even higher levels than serum. However, we did not find correlation between Gal1 levels and disease activity or disability. Therefore, our results suggest that Gal1 could be a diagnostic but not a severity biomarker.
The cardioprotective effects of the new crystal form of puerarin in isoproterenol-induced myocardial ischemia rats based on metabolomics
Authors: Zhou Yuzhi , Li Mengru , Song Jia , Shi Yongqiang , Qin Xuemei , Gao Zhaolin , Lv Yang , Du Guanhua
Published: October 2020

Puerarin has shown unique pharmacological effects on myocardial ischemia (MI). Changing the crystal form is an effective approach to improve the cardioprotective effects of puerarin. However, the mechanisms of the new crystal form of puerarin are unclear. In this study, an electrocardiogram, echocardiography, cardiac marker enzymatic activity, oxidative stress indices, and myocardial histology analysis of cardiac tissues were performed to evaluate the cardioprotective effects of the new crystal form of puerarin. Moreover, serum and cardiac tissue metabolomics based on nuclear magnetic resonance (NMR) were used to investigate the potential mechanism of the new crystal form. The results indicated that the new crystal form of puerarin (30 mg/kg) could improve oxidative stress indices, and these improvements were similar to those of the original crystal form of puerarin (120 mg/kg). The new crystal form of puerarin (30 mg/kg) could effectively improve the activities of cardiac marker enzymes, and the improvement effects were better than those of the original crystal form (120 mg/kg). Moreover, metabolomics analysis showed that amino acid metabolism, oxidative stress and energy metabolism were disturbed after MI and could be improved by puerarin. These results demonstrated that the new crystal form of puerarin was effective in treating MI.