bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolomics of sebum reveals lipid dysregulation in Parkinson’s disease
Authors: Sinclair Eleanor , Trivedi Drupad K. , Sarkar Depanjan , Walton-Doyle Caitlin , Milne Joy , Kunath Tilo , Rijs Anouk M. , de Bie Rob M. A. , Goodacre Royston , Silverdale Monty , Barran Perdita
Published: March 2021

Parkinson’s disease (PD) is a progressive neurodegenerative disorder, which is characterised by degeneration of distinct neuronal populations, including dopaminergic neurons of the substantia nigra. Here, we use a metabolomics profiling approach to identify changes to lipids in PD observed in sebum, a non-invasively available biofluid. We used liquid chromatography-mass spectrometry (LC-MS) to analyse 274 samples from participants (80 drug naïve PD, 138 medicated PD and 56 well matched control subjects) and detected metabolites that could predict PD phenotype. Pathway enrichment analysis shows alterations in lipid metabolism related to the carnitine shuttle, sphingolipid metabolism, arachidonic acid metabolism and fatty acid biosynthesis. This study shows sebum can be used to identify potential biomarkers for PD.
Biofilm formation in the lung contributes to virulence and drug tolerance of Mycobacterium tuberculosis
Authors: Chakraborty Poushali , Bajeli Sapna , Kaushal Deepak , Radotra Bishan Dass , Kumar Ashwani
Published: March 2021

Tuberculosis is a chronic disease that displays several features commonly associated with biofilm-associated infections: immune system evasion, antibiotic treatment failures, and recurrence of infection. However, although Mycobacterium tuberculosis (Mtb) can form cellulose-containing biofilms in vitro, it remains unclear whether biofilms are formed during infection in vivo. Here, we demonstrate the formation of Mtb biofilms in animal models of infection and in patients, and that biofilm formation can contribute to drug tolerance. First, we show that cellulose is also a structural component of the extracellular matrix of in vitro biofilms of fast and slow-growing nontuberculous mycobacteria. Then, we use cellulose as a biomarker to detect Mtb biofilms in the lungs of experimentally infected mice and non-human primates, as well as in lung tissue sections obtained from patients with tuberculosis. Mtb strains defective in biofilm formation are attenuated for survival in mice, suggesting that biofilms protect bacilli from the host immune system. Furthermore, the administration of nebulized cellulase enhances the antimycobacterial activity of isoniazid and rifampicin in infected mice, supporting a role for biofilms in phenotypic drug tolerance. Our findings thus indicate that Mtb biofilms are relevant to human tuberculosis.
Spin-state-dependent electrical conductivity in single-walled carbon nanotubes encapsulating spin-crossover molecules
Authors: Villalva Julia , Develioglu Aysegul , Montenegro-Pohlhammer Nicolas , Sánchez-de-Armas Rocío , Gamonal Arturo , Rial Eduardo , García-Hernández Mar , Ruiz-Gonzalez Luisa , Costa José Sánchez , Calzado Carmen J. , Pérez Emilio M. , Burzurí Enrique
Published: March 2021

Spin crossover (SCO) molecules are promising nanoscale magnetic switches due to their ability to modify their spin state under several stimuli. However, SCO systems face several bottlenecks when downscaling into nanoscale spintronic devices: their instability at the nanoscale, their insulating character and the lack of control when positioning nanocrystals in nanodevices. Here we show the encapsulation of robust Fe-based SCO molecules within the 1D cavities of single-walled carbon nanotubes (SWCNT). We find that the SCO mechanism endures encapsulation and positioning of individual heterostructures in nanoscale transistors. The SCO switch in the guest molecules triggers a large conductance bistability through the host SWCNT. Moreover, the SCO transition shifts to higher temperatures and displays hysteresis cycles, and thus memory effect, not present in crystalline samples. Our results demonstrate how encapsulation in SWCNTs provides the backbone for the readout and positioning of SCO molecules into nanodevices, and can also help to tune their magnetic properties at the nanoscale.
Asc-1 regulates white versus beige adipocyte fate in a subcutaneous stromal cell population
Authors: Suwandhi Lisa , Altun Irem , Karlina Ruth , Miok Viktorian , Wiedemann Tobias , Fischer David , Walzthoeni Thomas , Lindner Christina , Böttcher Anika , Heinzmann Silke S. , Israel Andreas , Khalil Ahmed Elagamy Mohamed Mahmoud , Braun Alexander , Pramme-Steinwachs Ines , Burtscher Ingo , Schmitt-Kopplin Philippe , Heinig Matthias , Elsner Martin , Lickert Heiko , Theis Fabian J. , Ussar Siegfried
Published: March 2021

Adipose tissue expansion, as seen in obesity, is often metabolically detrimental causing insulin resistance and the metabolic syndrome. However, white adipose tissue expansion at early ages is essential to establish a functional metabolism. To understand the differences between adolescent and adult adipose tissue expansion, we studied the cellular composition of the stromal vascular fraction of subcutaneous adipose tissue of two and eight weeks old mice using single cell RNA sequencing. We identified a subset of adolescent preadipocytes expressing the mature white adipocyte marker Asc-1 that showed a low ability to differentiate into beige adipocytes compared to Asc-1 negative cells in vitro. Loss of Asc-1 in subcutaneous preadipocytes resulted in spontaneous differentiation of beige adipocytes in vitro and in vivo. Mechanistically, this was mediated by a function of the amino acid transporter ASC-1 specifically in proliferating preadipocytes involving the intracellular accumulation of the ASC-1 cargo D-serine.
Calcium calmodulin kinase II activity is required for cartilage homeostasis in osteoarthritis
Authors: Nalesso Giovanna , Thorup Anne-Sophie , Eldridge Suzanne Elizabeth , De Palma Anna , Kaur Amanpreet , Peddireddi Kiran , Blighe Kevin , Rana Sharmila , Stott Bryony , Vincent Tonia Louise , Thomas Bethan Lynne , Bertrand Jessica , Sherwood Joanna , Fioravanti Antonella , Pitzalis Costantino , Dell’Accio Francesco
Published: March 2021

WNT ligands can activate several signalling cascades of pivotal importance during development and regenerative processes. Their de-regulation has been associated with the onset of different diseases. Here we investigated the role of the WNT/Calcium Calmodulin Kinase II (CaMKII) pathway in osteoarthritis. We identified Heme Oxygenase I (HMOX1) and Sox-9 as specific markers of the WNT/CaMKII signalling in articular chondrocytes through a microarray analysis. We showed that the expression of the activated form of CaMKII, phospho-CaMKII, was increased in human and murine osteoarthritis and the expression of HMOX1 was accordingly reduced, demonstrating the activation of the pathway during disease progression. To elucidate its function, we administered the CaMKII inhibitor KN93 to mice in which osteoarthritis was induced by resection of the anterior horn of the medial meniscus and of the medial collateral ligament in the knee joint. Pharmacological blockade of CaMKII exacerbated cartilage damage and bone remodelling. Finally, we showed that CaMKII inhibition in articular chondrocytes upregulated the expression of matrix remodelling enzymes alone and in combination with Interleukin 1. These results suggest an important homeostatic role of the WNT/CaMKII signalling in osteoarthritis which could be exploited in the future for therapeutic purposes.
Author Correction: Molecular mechanisms underlying the involvement of the sigma-1 receptor in methamphetamine-mediated microglial polarization
Authors: Chao Jie , Zhang Yuan , Du Longfei , Zhou Rongbin , Wu Xiaodong , Shen Kai , Yao Honghong
Published: March 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Value of CT features for predicting EGFR mutations and ALK positivity in patients with lung adenocarcinoma
Authors: Han Xiaoyu , Fan Jun , Li Yumin , Cao Yukun , Gu Jin , Jia Xi , Wang Yuhui , Shi Heshui
Published: March 2021

The aim of this study was to identify the relationships of epidermal growth factor receptor (EGFR) mutations and anaplastic large-cell lymphoma kinase (ALK) status with CT characteristics in adenocarcinoma using the largest patient cohort to date. In this study, preoperative chest CT findings prior to treatment were retrospectively evaluated in 827 surgically resected lung adenocarcinomas. All patients were tested for EGFR mutations and ALK status. EGFR mutations were found in 489 (59.1%) patients, and ALK positivity was found in 57 (7.0%). By logistic regression, the most significant independent prognostic factors of EGFR effective mutations were female sex, nonsmoker status, GGO air bronchograms and pleural retraction. For EGFR mutation prediction, receiver operating characteristic (ROC) curves yielded areas under the curve (AUCs) of 0.682 and 0.758 for clinical only or combined CT features, respectively, with a significant difference (p < 0.001). Furthermore, the exon 21 mutation rate in GGO was significantly higher than the exon 19 mutation rate(p = 0.029). The most significant independent prognostic factors of ALK positivity were age, solid-predominant-subtype tumours, mucinous lung adenocarcinoma, solid tumours and no air bronchograms on CT. ROC curve analysis showed that for predicting ALK positivity, the use of clinical variables combined with CT features (AUC = 0.739) was superior to the use of clinical variables alone (AUC = 0.657), with a significant difference (p = 0.0082). The use of CT features for patients may allow analyses of tumours and more accurately predict patient populations who will benefit from therapies targeting treatment.
Effect of co-inoculation with arbuscular mycorrhizal fungi and phosphate solubilizing fungi on nutrient uptake and photosynthesis of beach palm under salt stress environment
Authors: Zai Xue-Ming , Fan Jun-Jun , Hao Zhen-Ping , Liu Xing-Man , Zhang Wang-Xiang
Published: March 2021

Beach plum (Prunus maritima) is an ornamental plant, famous for its strong salt and drought stress tolerance. However, the poor growth rate of transplanted seedlings has seriously restricted its application in salinized soil. This study investigated the effects of inoculation with arbuscular mycorrhizal fungus (AMF), Funneliformis mosseae, and phosphate-solubilizing fungus (PSF), Apophysomyces spartima, on the growth, nutrient (N, P, and K) uptake, and photosynthesis of beach plum under saline (170 mM NaCl) and non-saline (0 mM NaCl) conditions. We aimed to find measures to increase the growth rate of beach plum in saline-alkali land and to understand the reasons for this increase. The results showed that salinization adversely affected colonization by AMF but positively increased PSF populations (increased by 33.9–93.3% over non-NaCl treatment). The dual application of AMF and PSF mitigated the effects of salt stress on all growth parameters and nutrient uptake, significantly for roots (dry weight and P and N contents increased by 91.0%, 68.9%, and 40%, respectively, over non-NaCl treatment). Salinization caused significant reductions in net photosynthetic rate (Pn), stomatal conductance (Gs), transpiration rate (E), and intercellular CO2 concentration (Ci) value, while inoculation with AMF and PSF inoculations significantly abated such reductions. The maximum efficiency of photosystem II (PSII) (Fv/Fm), the photochemical quenching coefficient (qP), and the nonphotochemical quenching (NPQ) values were affected little by inoculation with AMF, PSF, or both under non-NaCl treatments. However, plants inoculated with AMF and/or PSF had higher Fv/Fm, qP, and ФPSII values (increased by 72.5–188.1%) than the control under NaCl treatment, but not a higher NPQ value. We concluded that inoculation with AMF or PSF increased nutrient uptake and improved the gas-exchange and Chl fluorescence parameters of beach plum under salt stress environment. These effects could be strengthened by the combination of AMF and PSF, especially for nutrient uptake, root growth, and Pn, thereby alleviating the deleterious effects of NaCl stress on beach plum growth.
Premating barriers in young sympatric snail species
Authors: Maltseva Arina L. , Varfolomeeva Marina A. , Lobov Arseniy A. , Tikanova Polina O. , Repkin Egor A. , Babkina Irina Y. , Panova Marina , Mikhailova Natalia A. , Granovitch Andrei I.
Published: March 2021

Sympatric coexistence of recently diverged species raises the question of barriers restricting the gene flow between them. Reproductive isolation may be implemented at several levels, and the weakening of some, e.g. premating, barriers may require the strengthening of the others, e.g. postcopulatory ones. We analysed mating patterns and shell size of mates in recently diverged closely related species of the subgenus Littorina Neritrema (Littorinidae, Caenogastropoda) in order to assess the role of premating reproductive barriers between them. We compared mating frequencies observed in the wild with those expected based on relative densities using partial canonical correspondence analysis. We introduced the fidelity index (FI) to estimate the relative accuracy of mating with conspecific females and precopulatory isolation index (IPC) to characterize the strength of premating barriers. The species under study, with the exception of L. arcana, clearly demonstrated preferential mating with conspecifics. According to FI and IPC, L. fabalis and L. compressa appeared reliably isolated from their closest relatives within Neritrema. Individuals of these two species tend to be smaller than those of the others, highlighting the importance of shell size changes in gastropod species divergence. L. arcana males were often found in pairs with L. saxatilis females, and no interspecific size differences were revealed in this sibling species pair. We discuss the lack of discriminative mate choice in the sympatric populations of L. arcana and L. saxatilis, and possible additional mechanisms restricting gene flow between them.
Rapid coupling between solid earth and ice volume during the Quaternary
Authors: Kuwahara Yusuke , Yasukawa Kazutaka , Fujinaga Koichiro , Nozaki Tatsuo , Ohta Junichiro , Sato Honami , Kimura Jun-Ichi , Nakamura Kentaro , Yokoyama Yusuke , Kato Yasuhiro
Published: March 2021

The solid earth plays a major role in controlling Earth’s surface climate. Volcanic degassing of carbon dioxide (CO2) and silicate chemical weathering are known to regulate the evolution of climate on a geologic timescale (> 106 yr), but the relationship between the solid earth and the shorter (< 105 yr) fluctuations of Quaternary glacial–interglacial cycles is still under debate. Here we show that the seawater osmium isotope composition (187Os/188Os), a proxy for the solid earth’s response to climate change, has varied during the past 300,000 years in association with glacial–interglacial cycles. Our marine Os isotope mass-balance simulation reveals that the observed 187Os/188Os fluctuation cannot be explained solely by global chemical weathering rate changes corresponding to glacial–interglacial climate changes, but the fluctuation can be reproduced by taking account of short-term inputs of (1) radiogenic Os derived from intense weathering of glacial till during deglacial periods and (2) unradiogenic Os derived from enhanced seafloor hydrothermalism triggered by sea-level falls associated with increases of ice sheet volume. Our results constitute the first evidence that ice sheet recession and expansion during the Quaternary systematically and repetitively caused short-term (< 105 yr) solid earth responses via chemical weathering of glacial till and seafloor magmatism. This finding implies that climatic changes on < 105 yr timescales can provoke rapid feedbacks from the solid earth, a causal relationship that is the reverse of the longer-term (> 106 yr) causality that has been conventionally considered.
New estimate of chemical weathering rate in Xijiang River Basin based on multi-model
Authors: Zhang Yong , Yu Shi , He Shiyi , Sun Pingan , Wu Fu , Liu Zhenyu , Zhu Haiyan , Li Xiao , Zeng Peng
Published: March 2021

Hydrochemistry and Sr isotope compositions were measured in water samples collected during high- and low-water periods from the main stream and tributaries of the Xijiang River Basin in southern China. The primary weathering end-members were analyzed and calculated using the multi-model combination and classic hydrogeochemical method. During the high-water period, structural factors were found to be the main factors controlling chemical weathering in the basin, whereas anthropogenic activity and other random factors had a negligible influence. During the low-water period, both structural and random factors controlled chemical weathering. Through path-model and semi-variance analyses, we determined and quantified the relationship between the main weathering sources, whose results were stable; this is consistent with the inversion model. The total dissolved substances were mainly derived from carbonate weathering, which was approximately 76% (0–96%) while silicate weathering accounted for only 14% (5–19%). The inversion model results showed that the optimum silicate weathering rate was 7.264–35.551 × 103 mol/km2/year, where carbonic acid was the main factor that induces weathering. The CO2 flux consumed by rock weathering in the basin during the study period was 150.69 × 109 mol/year, while the CO2 flux consumed by carbonic acid weathering of carbonate (CCW) and silicate rocks (CSW) was 144.47 and 29.45 × 109 mol/year, respectively. The CO2 flux produced by H2SO4 weathered carbonate (SCW) was 23.23 × 109 mol/year.
DBnorm as an R package for the comparison and selection of appropriate statistical methods for batch effect correction in metabolomic studies
Authors: Bararpour Nasim , Gilardi Federica , Carmeli Cristian , Sidibe Jonathan , Ivanisevic Julijana , Caputo Tiziana , Augsburger Marc , Grabherr Silke , Desvergne Béatrice , Guex Nicolas , Bochud Murielle , Thomas Aurelien
Published: March 2021

As a powerful phenotyping technology, metabolomics provides new opportunities in biomarker discovery through metabolome-wide association studies (MWAS) and the identification of metabolites having a regulatory effect in various biological processes. While mass spectrometry-based (MS) metabolomics assays are endowed with high throughput and sensitivity, MWAS are doomed to long-term data acquisition generating an overtime-analytical signal drift that can hinder the uncovering of real biologically relevant changes. We developed “dbnorm”, a package in the R environment, which allows for an easy comparison of the model performance of advanced statistical tools commonly used in metabolomics to remove batch effects from large metabolomics datasets. “dbnorm” integrates advanced statistical tools to inspect the dataset structure not only at the macroscopic (sample batches) scale, but also at the microscopic (metabolic features) level. To compare the model performance on data correction, “dbnorm” assigns a score that help users identify the best fitting model for each dataset. In this study, we applied “dbnorm” to two large-scale metabolomics datasets as a proof of concept. We demonstrate that “dbnorm” allows for the accurate selection of the most appropriate statistical tool to efficiently remove the overtime signal drift and to focus on the relevant biological components of complex datasets.
Molecular imaging of a fluorescent antibody against epidermal growth factor receptor detects high-grade glioma
Authors: Zhou Quan , Vega Leonel Johana C. M. , Santoso Michelle Rai , Wilson Christy , van den Berg Nynke S. , Chan Carmel T. , Aryal Muna , Vogel Hannes , Cayrol Romain , Mandella Michael J. , Schonig Frank , Lu Guolan , Gambhir Sanjiv S. , Moseley Michael E. , Rosenthal Eben L. , Grant Gerald A.
Published: March 2021

The prognosis for high-grade glioma (HGG) remains dismal and the extent of resection correlates with overall survival and progression free disease. Epidermal growth factor receptor (EGFR) is a biomarker heterogeneously expressed in HGG. We assessed the feasibility of detecting HGG using near-infrared fluorescent antibody targeting EGFR. Mice bearing orthotopic HGG xenografts with modest EGFR expression were imaged in vivo after systemic panitumumab-IRDye800 injection to assess its tumor-specific uptake macroscopically over 14 days, and microscopically ex vivo. EGFR immunohistochemical staining of 59 tumor specimens from 35 HGG patients was scored by pathologists and expression levels were compared to that of mouse xenografts. Intratumoral distribution of panitumumab-IRDye800 correlated with near-infrared fluorescence and EGFR expression. Fluorescence distinguished tumor cells with 90% specificity and 82.5% sensitivity. Target-to-background ratios peaked at 14 h post panitumumab-IRDye800 infusion, reaching 19.5 in vivo and 7.6 ex vivo, respectively. Equivalent or higher EGFR protein expression compared to the mouse xenografts was present in 77.1% HGG patients. Age, combined with IDH-wildtype cerebral tumor, was predictive of greater EGFR protein expression in human tumors. Tumor specific uptake of panitumumab-IRDye800 provided remarkable contrast and a flexible imaging window for fluorescence-guided identification of HGGs despite modest EGFR expression.
EMeth: An EM algorithm for cell type decomposition based on DNA methylation data
Authors: Zhang Hanyu , Cai Ruoyi , Dai James , Sun Wei
Published: March 2021

We introduce a new computational method named EMeth to estimate cell type proportions using DNA methylation data. EMeth is a reference-based method that requires cell type-specific DNA methylation data from relevant cell types. EMeth improves on the existing reference-based methods by detecting the CpGs whose DNA methylation are inconsistent with the deconvolution model and reducing their contributions to cell type decomposition. Another novel feature of EMeth is that it allows a cell type with known proportions but unknown reference and estimates its methylation. This is motivated by the case of studying methylation in tumor cells while bulk tumor samples include tumor cells as well as other cell types such as infiltrating immune cells, and tumor cell proportion can be estimated by copy number data. We demonstrate that EMeth delivers more accurate estimates of cell type proportions than several other methods using simulated data and in silico mixtures. Applications in cancer studies show that the proportions of T regulatory cells estimated by DNA methylation have expected associations with mutation load and survival time, while the estimates from gene expression miss such associations.
Pattern discovery and disentanglement on relational datasets
Authors: Wong Andrew K. C. , Zhou Pei-Yuan , Butt Zahid A.
Published: March 2021

Machine Learning has made impressive advances in many applications akin to human cognition for discernment. However, success has been limited in the areas of relational datasets, particularly for data with low volume, imbalanced groups, and mislabeled cases, with outputs that typically lack transparency and interpretability. The difficulties arise from the subtle overlapping and entanglement of functional and statistical relations at the source level. Hence, we have developed Pattern Discovery and Disentanglement System (PDD), which is able to discover explicit patterns from the data with various sizes, imbalanced groups, and screen out anomalies. We present herein four case studies on biomedical datasets to substantiate the efficacy of PDD. It improves prediction accuracy and facilitates transparent interpretation of discovered knowledge in an explicit representation framework PDD Knowledge Base that links the sources, the patterns, and individual patients. Hence, PDD promises broad and ground-breaking applications in genomic and biomedical machine learning.
CDK1 is up-regulated by temozolomide in an NF-κB dependent manner in glioblastoma
Authors: Voce David J. , Bernal Giovanna M. , Cahill Kirk E. , Wu Longtao , Mansour Nassir , Crawley Clayton D. , Campbell Paige-Ashley S. , Arina Ainhoa , Weichselbaum Ralph R. , Yamini Bakhtiar
Published: March 2021

The alkylating agent, temozolomide (TMZ), is the most commonly used chemotherapeutic for the treatment of glioblastoma (GBM). The anti-glioma effect of TMZ involves a complex response that includes G2-M cell cycle arrest and cyclin-dependent kinase 1 (CDK1) activation. While CDK1 phosphorylation is a well-described consequence of TMZ treatment, we find that TMZ also robustly induces CDK1 expression. Analysis of this pathway demonstrates that CDK1 is regulated by NF-κB via a putative κB-site in its proximal promoter. CDK1 was induced in a manner dependent on mature p50 and the atypical inhibitor κB protein, BCL-3. Treatment with TMZ induced binding of NF-κB to the κB-site as assessed by gel shift analysis and chromatin immunoprecipitation. Examination of a CDK1 promoter-reporter demonstrated the functional relevance of the κB-site and underlined the requirement of p50 and BCL-3 for activation. Targeted knockdown of CDK1 or chemical inhibition with the selective CDK1 inhibitor, RO-3306, potentiated the cytotoxic effect of TMZ. These results identify CDK1 as an NF-κB target gene regulated by p50 and BCL-3 and suggest that targeting CDK1 may be a strategy to improve the efficacy of TMZ against GBM.
Proof-of-concept trial results of the HeartMan mobile personal health system for self-management in congestive heart failure
Authors: Clays Els , Puddu Paolo Emilio , Luštrek Mitja , Pioggia Giovanni , Derboven Jan , Vrana Marilena , De Sutter Johan , Le Donne Rita , Baert Anneleen , Bohanec Marko , Ciancarelli Maria Costanza , Dawodu Amos Adeyemo , De Pauw Michel , De Smedt Delphine , Marino Flavia , Pardaens Sofie , Schiariti Michele Salvatore , Valič Jakob , Vanderheyden Marc , Vodopija Aljoša , Tartarisco Gennaro
Published: March 2021

This study tested the effectiveness of HeartMan—a mobile personal health system offering decisional support for management of congestive heart failure (CHF)—on health-related quality of life (HRQoL), self-management, exercise capacity, illness perception, mental and sexual health. A randomized controlled proof-of-concept trial (1:2 ratio of control:intervention) was set up with ambulatory CHF patients in stable condition in Belgium and Italy. Data were collected by means of a 6-min walking test and a number of standardized questionnaire instruments. A total of 56 (34 intervention and 22 control group) participants completed the study (77% male; mean age 63 years, sd 10.5). All depression and anxiety dimensions decreased in the intervention group (p < 0.001), while the need for sexual counselling decreased in the control group (p < 0.05). Although the group differences were not significant, self-care increased (p < 0.05), and sexual problems decreased (p < 0.05) in the intervention group only. No significant intervention effects were observed for HRQoL, self-care confidence, illness perception and exercise capacity. Overall, results of this proof-of-concept trial suggest that the HeartMan personal health system significantly improved mental and sexual health and self-care behaviour in CHF patients. These observations were in contrast to the lack of intervention effects on HRQoL, illness perception and exercise capacity.
Shared cognitive mechanisms of hypnotizability with executive functioning and information salience
Authors: Faerman Afik , Spiegel David
Published: March 2021

In recent years, evidence linked hypnotizability to the executive control and information salience networks, brain structures that play a role in cognitive conflict resolution and perseveration (insisting on applying a previously learned logical rule on a new set). Despite the growing body of neuroimaging evidence, the cognitive phenotype of hypnotizability is not well understood. We hypothesized that higher hypnotizability would correspond to lower perseveration and set-shifting. Seventy-two healthy adults were tested for hypnotizability and executive functions (perseveration and set-shifting). Multiple regression analyses were performed to test the relationship between hypnotizability and perseveration and set-shifting. Higher hypnotizability was associated with lower perseveration after accounting for age and education. Hypnotizability significantly predicted perseveration but not set-shifting. Our results indicate an inverse relationship between trait hypnotizability and perseveration, an executive function that utilizes regions of both the executive control and the salience systems. This suggests that hypnotizability may share a common cognitive mechanism with error evaluation and implementation of logical rules.
Increases in Great Lake winds and extreme events facilitate interbasin coupling and reduce water quality in Lake Erie
Authors: Jabbari Aidin , Ackerman Josef D. , Boegman Leon , Zhao Yingming
Published: March 2021

Climate change affects physical and biogeochemical processes in lakes. We show significant increases in surface-water temperature (~ 0.5 °C decade−1; > 0.2% year−1) and wave power (> 1% year−1; the transport of energy by waves) associated with atmospheric phenomena (Atlantic Multidecadal Oscillation and Multivariate El Niño/Southern Oscillation) in the month of August between 1980 and 2018 in the Laurentian Great Lakes. A pattern in wave power, in response to extreme winds, was identified as a proxy to predict interbasin coupling in Lake Erie. This involved the upwelling of cold and hypoxic (dissolved oxygen < 2 mg L−1) hypolimnetic water containing high total phosphorus concentration from the seasonally stratified central basin into the normally well-mixed western basin opposite to the eastward flow. Analysis of historical records indicate that hypoxic events due to interbasin exchange have increased in the western basin over the last four decades (43% in the last 10 years) thus affecting the water quality of the one of the world’s largest freshwater sources and fisheries.
Perspective taking as a mechanism for children’s developing preferences for equitable distributions
Authors: Sobel David M. , Blankenship Jayd
Published: March 2021

How do young children develop a concept of equity? Infants prefer dividing resources equally and expect others to make such distributions. Between the ages of 3–8, children begin to exhibit preferences to avoid inequitable outcomes in their distributions, dividing resources unequally if the result of that distribution is a more equitable outcome. Four studies investigated children’s developing preferences for generating equitable distributions, focusing on the mechanisms for this development. Children were presented with two characters with different amount of resources, and then a third character who will distribute more resources to them. Three- to 8-year-olds were asked whether the third character should give an equal number of resources to the recipients, preserving the inequity, or an unequal number to them, creating an equitable outcome. Starting at age 7, children showed a preference for equitable distributions (Study 1, N = 144). Studies 2a (N = 72) and 2b (N = 48) suggest that this development is independent of children’s numerical competence. When asked to take the perspective of the recipient with fewer resources, 3- to 6-year-olds were more likely to make an equitable distribution (Study 3, N = 122). These data suggest that social perspective taking underlies children’s prosocial actions, and supports the hypothesis that their spontaneous capacity to take others’ perspectives develops during the early elementary-school years.
A meta-analysis of Watson for Oncology in clinical application
Authors: Jie Zhou , Zhiying Zeng , Li Li
Published: March 2021

Using the method of meta-analysis to systematically evaluate the consistency of treatment schemes between Watson for Oncology (WFO) and Multidisciplinary Team (MDT), and to provide references for the practical application of artificial intelligence clinical decision-support system in cancer treatment. We systematically searched articles about the clinical applications of Watson for Oncology in the databases and conducted meta-analysis using RevMan 5.3 software. A total of 9 studies were identified, including 2463 patients. When the MDT is consistent with WFO at the ‘Recommended’ or the ‘For consideration’ level, the overall concordance rate is 81.52%. Among them, breast cancer was the highest and gastric cancer was the lowest. The concordance rate in stage I–III cancer is higher than that in stage IV, but the result of lung cancer is opposite (P < 0.05).Similar results were obtained when MDT was only consistent with WFO at the "recommended" level. Moreover, the consistency of estrogen and progesterone receptor negative breast cancer patients, colorectal cancer patients under 70 years old or ECOG 0, and small cell lung cancer patients is higher than that of estrogen and progesterone positive breast cancer patients, colorectal cancer patients over 70 years old or ECOG 1–2, and non-small cell lung cancer patients, with statistical significance (P < 0.05). Treatment recommendations made by WFO and MDT were highly concordant for cancer cases examined, but this system still needs further improvement. Owing to relatively small sample size of the included studies, more well-designed, and large sample size studies are still needed.
Genetic structure of Malus sylvestris and potential link with preference/performance by the rosy apple aphid pest Dysaphis plantaginea
Authors: Denoirjean Thomas , Doury Géraldine , Cornille Amandine , Chen Xilong , Hance Thierry , Ameline Arnaud
Published: March 2021

The European crabapple Malus sylvestris, a crop wild relative of Malus domestica, is a major contributor to the cultivated apple genome and represents a potential source of interesting alleles or genes, particularly pest resistance traits. An original approach was used to explore the trophic interaction between M. sylvestris populations and its pest, the rosy apple aphid (Dysaphis plantaginea). Using 13 microsatellite markers, population genetic structure and level of crop-to-wild introgressions were inferred between M. sylvestris seedlings from three sites in Europe (Denmark, France, Romania), and M. domestica seedlings. Genetically characterized plants were also used to analyze aphid feeding behavior and fitness parameters. First, aphids submitted to two genetically close M. sylvestris populations (the Danish and French) exhibited similar behavioral parameters, suggesting similar patterns of resistance in these host plants. Second, the Romanian M. sylvestris population was most closely genetically related to M. domestica. Although the two plant genetic backgrounds were significantly differentiated, they showed comparable levels of sensitivity to D. plantaginea infestation. Third, aphid fitness parameters were not significantly impacted by the host plant’s genetic background. Finally, crop-to-wild introgression seemed to significantly drive resistance to D. plantaginea independent of host plant population genetic structure, with hybrids being less suitable hosts.
Systems-wide effects of short-term feed deprivation in obese mice
Authors: Andersen Daniel , Roager Henrik Munch , Zhang Li , Moll Janne Marie , Frandsen Henrik Lauritz , Danneskiold-Samsøe Niels Banhos , Hansen Axel Kornerup , Kristiansen Karsten , Licht Tine Rask , Brix Susanne
Published: March 2021

While prolonged fasting induces significant metabolic changes in humans and mice, less is known about systems-wide metabolic changes in response to short-term feed deprivation, which is used in experimental animal studies prior to metabolic challenge tests. We here performed a systems biology-based investigation of connections between gut bacterial composition and function, inflammatory and metabolic parameters in the intestine, liver, visceral adipose tissue, blood and urine in high-fat fed, obese mice that were feed deprived up to 12 h. The systems-wide analysis revealed that feed deprivation linked to enhanced intestinal butyric acid production and expression of the gene encoding the pro-thermogenic uncoupling protein UCP1 in visceral adipose tissue of obese mice. Ucp1 expression was also positively associated with Il33 expression in ileum, colon and adipose tissue as well as with the abundance of colonic Porphyromonadaceae, the latter also correlating to cecal butyric acid levels. Collectively, the data highlighted presence of a multi-tiered system of inter-tissue communication involving intestinal, immune and metabolic functions which is affected by feed deprivation in obese mice, thus pointing to careful use of short-feed deprivation in metabolic studies using obese mice.
Combined nicotinamide N-methyltransferase inhibition and reduced-calorie diet normalizes body composition and enhances metabolic benefits in obese mice
Authors: Sampson Catherine M. , Dimet Andrea L. , Neelakantan Harshini , Ogunseye Kehinde O. , Stevenson Heather L. , Hommel Jonathan D. , Watowich Stanley J.
Published: March 2021

Obesity is a large and growing global health problem with few effective therapies. The present study investigated metabolic and physiological benefits of nicotinamide N-methyltransferase inhibitor (NNMTi) treatment combined with a lean diet substitution in diet-induced obese mice. NNMTi treatment combined with lean diet substitution accelerated and improved body weight and fat loss, increased whole-body lean mass to body weight ratio, reduced liver and epididymal white adipose tissue weights, decreased liver adiposity, and improved hepatic steatosis, relative to a lean diet substitution alone. Importantly, combined lean diet and NNMTi treatment normalized body composition and liver adiposity parameters to levels observed in age-matched lean diet control mice. NNMTi treatment produced a unique metabolomic signature in adipose tissue, with predominant increases in ketogenic amino acid abundance and alterations to metabolites linked to energy metabolic pathways. Taken together, NNMTi treatment’s modulation of body weight, adiposity, liver physiology, and the adipose tissue metabolome strongly support it as a promising therapeutic for obesity and obesity-driven comorbidities.
MAGI1 inhibits the AMOTL2/p38 stress pathway and prevents luminal breast tumorigenesis
Authors: Kantar Diala , Mur Emilie Bousquet , Mancini Maicol , Slaninova Vera , Salah Yezza Ben , Costa Luca , Forest Elodie , Lassus Patrice , Géminard Charles , Boissière-Michot Florence , Orsetti Béatrice , Theillet Charles , Colinge Jacques , Benistant Christine , Maraver Antonio , Heron-Milhavet Lisa , Djiane Alexandre
Published: March 2021

Alterations to cell polarization or to intercellular junctions are often associated with epithelial cancer progression, including breast cancers (BCa). We show here that the loss of the junctional scaffold protein MAGI1 is associated with bad prognosis in luminal BCa, and promotes tumorigenesis. E-cadherin and the actin binding scaffold AMOTL2 accumulate in MAGI1 deficient cells which are subjected to increased stiffness. These alterations are associated with low YAP activity, the terminal Hippo-pathway effector, but with an elevated ROCK and p38 Stress Activated Protein Kinase activities. Blocking ROCK prevented p38 activation, suggesting that MAGI1 limits p38 activity in part through releasing actin strength. Importantly, the increased tumorigenicity of MAGI1 deficient cells is rescued in the absence of AMOTL2 or after inhibition of p38, demonstrating that MAGI1 acts as a tumor-suppressor in luminal BCa by inhibiting an AMOTL2/p38 stress pathway.
Genetic dissection of down syndrome-associated alterations in APP/amyloid-β biology using mouse models
Authors: Tosh Justin L. , Rhymes Elena R. , Mumford Paige , Whittaker Heather T. , Pulford Laura J. , Noy Sue J. , Cleverley Karen ,   LonDownS Consortium, Strydom Andre , Fisher Elizabeth , Wiseman Frances , Nizetic Dean , Hardy John , Tybulewicz Victor , Karmiloff-Smith Annette , Walker Matthew C. , Tybulewicz Victor L. J. , Wykes Rob C. , Fisher Elizabeth M. C. , Wiseman Frances K.
Published: March 2021

Individuals who have Down syndrome (caused by trisomy of chromosome 21), have a greatly elevated risk of early-onset Alzheimer’s disease, in which amyloid-β accumulates in the brain. Amyloid-β is a product of the chromosome 21 gene APP (amyloid precursor protein) and the extra copy or ‘dose’ of APP is thought to be the cause of this early-onset Alzheimer’s disease. However, other chromosome 21 genes likely modulate disease when in three-copies in people with Down syndrome. Here we show that an extra copy of chromosome 21 genes, other than APP, influences APP/Aβ biology. We crossed Down syndrome mouse models with partial trisomies, to an APP transgenic model and found that extra copies of subgroups of chromosome 21 gene(s) modulate amyloid-β aggregation and APP transgene-associated mortality, independently of changing amyloid precursor protein abundance. Thus, genes on chromosome 21, other than APP, likely modulate Alzheimer’s disease in people who have Down syndrome.
Higher choroidal thickness and lower choriocapillaris blood flow signal density based on optical coherence tomography angiography in diabetics
Authors: Zhang Yaoli , Qin Yuanjun , Wang Shuaishuai , Liu Yuyan , Li Xinyu , Sun Xufang
Published: March 2021

Diabetes mellitus (DM) is one of the fastest growing chronic diseases in the world and one of the main causes of vision loss. Whether or not diabetic choroidopathy (DC) is involved in the initiation and progression of diabetic ocular complications needs to be explored. We included 54 diabetic eyes from 36 diabetic patients, and 54 healthy eyes from 32 control subjects after propensity scores matching. All of the subjects were given pupil light and dark adaptation examination and optical coherence tomography angiography (OCTA). Scotopic pupil diameter (SPD), pupil contraction amplitude, and velocity of pupil contraction of the diabetic group were significantly lower than that of the healthy control group (P < 0.05).Choroidal thickness at temporal quadrant (at 750 μm) and superior quadrant (at 1500 μm and 2250 μm) increased in diabetic group compared to control group(P < 0.05).In the diabetic group, choriocapillaris blood flow signal density (CCBFSD) in the macular area (diameter = 2000 μm) were significantly decreased compared with the healthy control group (P < 0.05). Apparent changes in pupil and choroidal blood flow were observed in the diabetic patients.
Metallic conduction through van der Waals interfaces in ultrathin $$\hbox{Bi}_2\hbox{Te}_3$$ films
Authors: Hatta Shinichiro , Obayashi Ko , Okuyama Hiroshi , Aruga Tetsuya
Published: March 2021

While the van der Waals (vdW) interface in layered materials hinders the transport of charge carriers in the vertical direction, it serves a good horizontal conduction path. We have investigated electrical conduction of few quintuple-layer (QL) $$\hbox {Bi}_2\hbox {Te}_3$$

Bi
2

Te
3

films by in situ four-point probe conductivity measurement. The impact of the vdW (Te–Te) interface appeared as a large conductivity increase with increasing thickness from 1 to 2 QL. Angle-resolved photoelectron spectroscopy and first-principles calculations reveal the confinement of bulk-like conduction band (CB) state into the vdW interface. Our analysis based on the Boltzmann equation showed that the conduction of the CB has a long mean free path compared to the surface-state conduction. This is mainly attributed to the spatial separation of the CB electrons and the donor defects located at the Bi sites.
Publisher Correction: Microbiota analysis and transient elastography reveal new extra-hepatic components of liver steatosis and fibrosis in obese patients
Authors: Lanthier Nicolas , Rodriguez Julie , Nachit Maxime , Hiel Sophie , Trefois Pierre , Neyrinck Audrey M. , Cani Patrice D. , Bindels Laure B. , Thissen Jean-Paul , Delzenne Nathalie M.
Published: March 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
A new bioinformatics approach identifies overexpression of GRB2 as a poor prognostic biomarker for prostate cancer
Authors: Iwata Teppei , Sedukhina Anna S. , Kubota Manabu , Oonuma Shigeko , Maeda Ichiro , Yoshiike Miki , Usuba Wataru , Minagawa Kimino , Hames Eleina , Meguro Rei , Cho Sunny , Chien Stephen H. H. , Urabe Shiro , Pae Sookhee , Palanisamy Kishore , Kumai Toshio , Yudo Kazuo , Kikuchi Eiji , Sato Ko
Published: March 2021

A subset of prostate cancer displays a poor clinical outcome. Therefore, identifying this poor prognostic subset within clinically aggressive groups (defined as a Gleason score (GS) ≧8) and developing effective treatments are essential if we are to improve prostate cancer survival. Here, we performed a bioinformatics analysis of a TCGA dataset (GS ≧8) to identify pathways upregulated in a prostate cancer cohort with short survival. When conducting bioinformatics analyses, the definition of factors such as “overexpression” and “shorter survival” is vital, as poor definition may lead to mis-estimations. To eliminate this possibility, we defined an expression cutoff value using an algorithm calculated by a Cox regression model, and the hazard ratio for each gene was set so as to identify genes whose expression levels were associated with shorter survival. Next, genes associated with shorter survival were entered into pathway analysis to identify pathways that were altered in a shorter survival cohort. We identified pathways involving upregulation of GRB2. Overexpression of GRB2 was linked to shorter survival in the TCGA dataset, a finding validated by histological examination of biopsy samples taken from the patients for diagnostic purposes. Thus, GRB2 is a novel biomarker that predicts shorter survival of patients with aggressive prostate cancer (GS ≧8).
First description of a widespread Mytilus trossulus-derived bivalve transmissible cancer lineage in M. trossulus itself
Authors: Skazina Maria , Odintsova Nelly , Maiorova Maria , Ivanova Angelina , Väinölä Risto , Strelkov Petr
Published: March 2021

Two lineages of bivalve transmissible neoplasia (BTN), BTN1 and BTN2, are known in blue mussels Mytilus. Both lineages derive from the Pacific mussel M. trossulus and are identified primarily by their unique genotypes of the nuclear gene EF1α. BTN1 is found in populations of M. trossulus from the Northeast Pacific, while BTN2 has been detected in populations of other Mytilus species worldwide but not in M. trossulus itself. Here we examined M. trossulus from the Sea of Japan (Northwest Pacific) for the presence of BTN. Using hemocytology and flow cytometry of the hemolymph, we confirmed the presence of disseminated neoplasia in our specimens. Cancerous mussels possessed the BTN2 EF1α genotype and two mitochondrial haplotypes with different recombinant control regions, similar to that of common BTN2 lineages. This is the first report of BTN2 in its original host species M. trossulus. A comparison of all available BTN and M. trossulus COI sequences suggests a common and recent origin of BTN2 diversity in populations of M. trossulus outside the Northeast Pacific, possibly in the Northwest Pacific.
New diagonal micropolarizer arrays designed by an improved model in fourier domain
Authors: Hao Jia , Wang Yan , Zhou Kui , Yu Xiaochang , Yu Yiting
Published: March 2021

The design of micropolarizer array (MPA) patterns in Fourier domain provides an efficient approach to reconstruct and investigate the polarization information. Inspired by Alenin’s works, in this paper, we propose an improved design model to cover both 2 × N MPAs and other original MPAs, by which an entirely new class of MPA patterns is suggested. The performance of the new patterns is evaluated through Fourier domain analysis and numerical simulations compared with the existing MPAs. Particularly, we analyze the reconstruction accuracy of the first three Stokes parameters and degree of linear polarization (DoLP) in detail. The experimental results confirm that the 2 × 2 × 2 MPA provides the highest reconstruction quality of s0, s1, s2 and DoLP in terms of quantitative measures and visual quality, while the 3 × 3 diagonal MPA achieves the state-of-the-art best results in case of single-snapshot systems. The guidance of this extended model and new diagonal MPAs show its massive potential for the division of focal plane (DoFP) polarization imaging applications.