bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical characteristics and antibody response to SARS-CoV-2 spike 1 protein using VITROS Anti-SARS-CoV-2 antibody tests in COVID-19 patients in Japan
Authors: Nagura-Ikeda Mayu , Imai Kazuo , Kubota Katsumi , Noguchi Sakiko , Kitagawa Yutaro , Matsuoka Masaru , Tabata Sakiko , Miyoshi Kazuyasu , Ito Toshimitsu , Tamura Kaku , Maeda Takuya
Published: April 2021

Introduction. Serological tests for COVID-19 are important in providing results for surveillance and supporting diagnosis. Investigating the serological response in COVID-19 patients with different disease severity is important for assessing the clinical utility of serological assays.

Gap Statement. However, few studies have investigated the clinical utility of antibody assays for COVID-19 or differences in antibody response in association with disease severity.

Aim. The study aimed to evaluate the clinical characteristics and clinical utility of VITROS SARS-CoV-2 antibody tests according to COVID-19 severity in patients in Japan.

Methodology. We analysed 255 serum specimens from 130 COVID-19 patients and examined clinical records and laboratory data. Presence of total (IgA, IgM, and IgG) and specific IgG antibody for the spike 1 antigen of SARS-CoV-2 was determined using VITROS Anti-SARS-CoV-2 antibody tests.

Results. Overall, 98 (75.4 %) and 32 (24.6 %) patients had mild and severe COVID-19, respectively. On admission, 76 (58.5 %) and 45 (34.6 %) patients were positive for total and IgG antibody assays. Among 91 patients at discharge, 90 (98.9 %) and 81 (89.0 %) were positive for total and IgG antibody, respectively. Clinical background and laboratory findings on admission, but not the prevalence or concentration of total or IgG antibody, were associated with disease prognosis. Total and IgG antibody intensities were significantly higher in severe cases than in mild cases in serum collected >11 days after onset, but not within 10 days.

Conclusion. VITROS Anti-SARS-CoV-2 total and IgG assays will be useful as supporting diagnostic and surveillance tools and for evaluation of humoral immune response to COVID-19. Optimal prediction of disease prognosis is made from considering both clinical history and laboratory findings.
Strong anti-viral responses in pediatric COVID-19 patients in South Brazil
Authors: Fazolo Tiago , Lima Karina , Fontoura Julia C. , de Souza Priscila Oliveira , Hilario Gabriel , Zorzetto Renata , Júnior Luiz Rodrigues , Pscheidt Veridiane Maria , de Castilhos Ferreira Neto Jayme , Haubert Alisson F. , Gambin Izza , Oliveira Aline C. , Mello Raissa S. , de Bastos Balbe e Gutierres Matheus , Gassen Rodrigo Benedetti , Sauthier Sartor Ivaine Tais , Zavaglia Gabriela Oliveira , Fernandes Ingrid Rodrigues , Varela Fernanda Hammes , Polese-Bonatto Márcia , Borges Thiago J. , Callegari-Jacques Sidia Maria , da Costa Marcela Santos Correa , de Araujo Schwartz Jaqueline , Scotta Marcelo Comerlato , Stein Renato T. , Bonorino Cristina
Published: April 2021

Epidemiological evidence that COVID-19 manifests as a milder disease in children compared to adults has been reported by numerous studies, but the mechanisms underlying this phenomenon have not been characterized. It is still unclear how frequently children get infected, and/or generate immune responses to SARS-CoV-2. We have performed immune profiling of pediatric and adult COVID-19 patients in Brazil, producing over 38 thousand data points, asking if cellular or humoral immune responses could help explain milder disease in children. In this study, pediatric COVID-19 patients presented high viral titers. Though their non-specific immune profile was dominated by naive, non-activated lymphocytes, their dendritic cells expressed high levels of HLA-DR and were low in CX3CR1, indicating competence to generate immune responses that are not targeted to inflamed tissue. Finally, children formed strong specific antibody and T cell responses for viral structural proteins. Children’s T cell responses differed from adults in that their CD8+ TNFα+ T cell responses were low for S peptide but significantly higher against N and M peptide pools. Altogether, our data support a scenario in which SARS-CoV-2 infected children may contribute to transmission, though generating strong and differential responses to the virus that might associate with protection in pediatric COVID-19 presentation.
Just Say No to Postmortem Drug Dose Calculations
Authors: Maskell Peter D
Published: April 2021

It has long been known that forensic and clinical toxicologists should not determine the dose of a drug administered based on postmortem blood drug concentrations but to date there has been limited information as to how unreliable these dose calculations can be. Using amitriptyline as a model drug this study used the empirically determined pharmacokinetic variables for amitriptyline from clinical studies and clinical, overdose (where the individual survived) and death (ascribed to amitriptyline toxicity) case studies in which the dose of drug administered or taken was known. Using these data, standard pharmacokinetic equations and general error propagation it was possible to estimate the accuracy of the consumed dose of amitriptyline compared to the actual dose consumed. As was expected in postmortem cases, depending on the pharmacokinetic equation used, the accuracy (mean +128 to +2347 %) and precision (SD ± 383 to 3698%) were too large to allow reliable estimation of the dose of drug taken or administered prior to death based on postmortem blood drug concentrations. This work again reinforces that dose calculations from postmortem blood drug concentrations should not be carried out.
A multiscale model predicts the sensitivity ofChlorella vulgaristo light and nitrogen levels in photobioreactors
Authors: Tibocha-Bonilla Juan D. , Zuniga Cristal , Broddrick Jared T. , Zengler Karsten , Godoy-Silva Rubén D.
Published: April 2021

The maximization of lipid productivity in microalgae is crucial for the biofuel industry, and it can be achieved by manipulating their metabolism. However, little efforts have been made to apply metabolic models in a dynamic framework to predict possible outcomes to scenarios observed at an industrial scale. Here, we present a dynamic framework for the simulation of large-scale photobioreactors. The framework was generated by merging the genome-scale metabolic model ofChlorella vulgaris(iCZ843) with reactor-scale parameters, thus yielding a multiscale model. This multiscale model was employed to predict the sensitivity of growth and composition variation ofC. vulgarison light and nitrogen levels. Simulations of lipid accumulation quantified the tradeoff between growth and lipid biosynthesis under nitrogen limitation. Moreover, our modeling approach quantitatively predicted the dependence of microalgal metabolism on light intensity and circadian oscillations. Finally, we use the model to design a reactor irradiance profile that maximized lipid accumulation, thus achieving a lipid productivity increase of 46% at a constant intensity of 966 μE m−2s−1. Our modeling framework elucidated how metabolism and external factors can be combined to predict optimized parameters for industrial applications.
Methylation of 23S rRNA G748 and the ribosomal protein L22 Lys-94 are critical factors for maintaining the association between ribosome stalling and proteome composition inStreptococcus pneumoniae
Authors: Shoji Tatsuma
Published: April 2021

Background

23S rRNA modification located at the nascent peptides exit tunnel plays an important role in both translation processes and the binding of the antibiotics. Methylation of the guanine at position 748 (m1G748) in 23S rRNA inStreptococcus pneumoniaeis involved in the ribosome stalling and the binding of the antibiotic telithromycin (TEL). The disruption of the gene encoding RlmAIIwhich methylates 23S rRNA G748 results in the increased resistance of TEL inS. pneumoniae. However, an isolated high-level TEL-resistantS. pneumoniaestrain indicated that additional undescribed factors were involved in TEL resistance inS. pneumoniae.

Results

We successfully isolated a high-level TEL-resistantS. pneumoniaeRlmAIImutant and determined the whole-genome sequence. The lysine residue at the position 94 in ribosomal protein 22 (L22 K94) was critical in binding of TEL to the ribosome. A growth competition assay showed that L22 K94 was required for the function of m1G748. Ribosome profiling revealed that m1G748 and L22 K94 were both essential to maintain the relationship between the ribosome stalling and proteome composition.

Conclusion

InS. pneumoniae, the combination of methylation status of G748 and the residue at position 94 in L22 are essential for both the distribution of ribosome stalling and the binding of TEL to ribosomes.
Isolation, screening, degradation characteristics of a quinclorac-degrading bacteria D and its potential of bioremediation for rice field environment polluted by quinclorac
Authors: Huang Siqi , Pan Jiuyue , Tuwang Mancuo , Li Hongyan , Ma Chenyi , Chen Mingxue , Lin Xiaoyan
Published: April 2021

Quinclorac (QNC) is a highly selective, hormonal, and low-toxic herbicide with a long duration. And the growth and development of subsequent crops are easily affected by QNC accumulated in the soil. In this paper, a QNC-degrading strain D was isolated and screened from the rice paddy soil. Through morphology, physiological and biochemical tests and 16Sr DNA gene analysis, strain D was identified asCellulosimicrobium cellulanssp. And the QNC degradation characteristics of strain D were studied. Under the optimal culture conditions, the QNC-degrading rate was 45.9% after culturing for 21 days. The QNC-degrading efficiency of strain D in the field was evaluated by a simulated pot experiment. The results show that strain D can promote the growth of rice and QNC-degrading effectively. This research could provide a new bacterial species for microbial degradation of QNC and lay a theoretical foundation for further research on QNC remediation.

Importance

At present, some QNC-degrading bacteria have been isolated from different environments, but there are no reports ofCellulosimicrobium cellulanssp. bacterial that could degrade QNC. In this study, a new QNC-degradation strain was selected from the paddy soil. The degradation characteristics of strain D were studied in detail. The results shown that strain D had a satisfactory quinclorac-degrading efficiency. Two degradation products of QNC by strain D were identified by HPLC-Q-TOF/MS: 3-pyridylacetic acid (138.0548 m/z) and 3-ethylpyridine (108.0805 m/z), which have not been reported before. The strain D had a potential ability of quinclorac-degrading effectively in the quinclorac-polluted paddy field environment.
Clp protease and antisense RNA jointly regulate the global regulator CarD to mediate mycobacterial starvation response
Authors: Li Xinfeng , Chen Fang , Liu Xiaoyu , Xiao Jinfeng , Andongma Binda T. , Tang Qing , Cao Xiaojian , Chou Shan-Ho , Galperin Michael Y. , He Jin
Published: April 2021

Under starvation conditions, bacteria tend to slow down their translation rate by reducing rRNA synthesis, but the way they accomplish that may vary in different bacteria. InMycobacteriumspecies, transcription of rRNA is activated by the RNA polymerase (RNAP) accessory transcription factor CarD, which interacts directly with RNAP to stabilize the RNAP-promoter open complex formed on rRNA genes. The functions of CarD have been extensively studied, but the mechanisms that control its expression remain obscure. Here, we report that the level of CarD was tightly regulated when mycobacterial cells switched from nutrient-rich to nutrient-deprived conditions. At the translational level, an antisense RNA ofcarD(AscarD) was induced in a SigF-dependent manner to bind withcarDmRNA and inhibit CarD translation, while at the post-translational level, the residual intracellular CarD was quickly degraded by the Clp protease. AscarD thus worked synergistically with Clp protease to decrease the CarD level to help mycobacterial cells cope with the nutritional stress. Altogether, our work elucidates the regulation mode of CarD and delineates a new mechanism for the mycobacterial starvation response, which is important for the adaptation and persistence of mycobacterial pathogens in the host environment.
Loss of adipocyte phospholipase genePLAAT3causes lipodystrophy and insulin resistance due to inactivated arachidonic acid-mediated PPARγsignaling
Authors: Schuermans Nika , Chehadeh Salima El , Hemelsoet Dimitri , Bogaert Elke , Debackere Elke , Hilbert Pascale , Van Doninck Nike , Taquet Marie-Caroline , Rosseel Toon , De Clercq Griet , Van Haverbeke Carole , Chanson Jean-Baptiste , Funalot Benoit , Authier François-Jérôme , Kaya Sabine , Terryn Wim , Callens Steven , Depypere Bernard , Van Dorpe Jo ,   Program for Undiagnosed Diseases (UD-PrOZA), Poppe Bruce , Depienne Christel , Dermaut Bart
Published: April 2021

PLAAT3 is a phospholipid modifying enzyme predominantly expressed in white adipose tissue (WAT). It is a candidate drug target as Plaat3 deficiency in mice protects against picornavirus infection and diet-induced obesity. We identified four patients with homozygous loss-of-function mutations inPLAAT3, presenting with partial lipodystrophy, severe insulin resistance and dyslipidemia. PLAAT3-deficient WAT showed a failure to liberate arachidonic acid (AA) from membrane phospholipids resulting in an inactive gene network downstream of adipogenesis master regulator and anti-diabetic drug target PPARG. These findings establish PLAAT3 deficiency in humans as a novel type of partial lipodystrophy due to an AA- and PPARG-dependent defect in WAT differentiation and function.
Human myelin protein P2: From crystallography to time-lapse membrane imaging and neuropathy-associated variants
Authors: Uusitalo Maiju , Berg Klenow Martin , Laulumaa Saara , Blakeley Matthew P. , Simonsen Adam Cohen , Ruskamo Salla , Kursula Petri
Published: April 2021

Peripheral myelin protein 2 (P2) is a fatty acid-binding protein expressed in vertebrate peripheral nervous system myelin, as well as in human astrocytes. Suggested functions of P2 include membrane stacking and lipid transport. Mutations in the PMP2 gene, encoding P2, are associated with Charcot-Marie-Tooth disease (CMT). Recent studies have revealed three novel PMP2 mutations in CMT patient families. To shed light on the structure and function of the corresponding P2 variants, we used X-ray and neutron crystallography, small-angle X-ray scattering, circular dichroism spectroscopy, computer simulations, and lipid binding assays. The crystal and solution structures of the I50del, M114T, and V115A variants of P2 showed only minor differences to the wild-type protein, whereas the thermal stability of the disease variants was reduced. Lipid vesicle aggregation assays revealed no change in membrane stacking characteristics, while the variants showed slightly altered fatty acid binding. Time-lapse imaging of lipid bilayers indicated membrane blebbing induced by P2, which could be related to its function in stacking of two curved membrane surfaces in myelin in vivo. All variants caused blebbing of membranes on similar timescales. In order to better understand the links between structure, dynamics, and function, the crystal structure of perdeuterated P2 was refined from room temperature data collected using both neutrons and X-rays, and the results were compared to molecular dynamics simulations and cryocooled crystal structures. Taken together, our data indicate similar properties of all known CMT variants of human P2; while crystal structures are nearly identical, stability and function of the disease variants are impaired compared to the wild-type protein. Our data provide new insights into the structure-function relationships and dynamics of P2 in health and disease.
Subjective understanding of actions and emotions requires interaction of the semantic and action observation networks
Authors: Zhan Minye , Goebel Rainer , de Gelder Beatrice
Published: April 2021

Previous studies have investigated the neural basis of action and emotion perception conveyed by whole body postures and movements. However, subjective understanding of other people’s bodily actions and emotions, raises different issues that are currently not well understood and have so far seldom been investigated. In this 7T fMRI study, we proceeded beyond conventional univariate/multivariate analyses with predefined categories, and examined the representational geometry of subjective action- and emotion-understanding by mapping individual subjective reports with word embeddings. Dimensionality reduction revealed that the representations for perceived action and emotion were high dimensional, each correlated to but were not reducible to the predefined action and emotion categories. Searchlight representational similarity analysis showed that the representations in the left middle superior temporal sulcus and left dorsal premotor cortex corresponded to the subjective action and emotion understanding of the participants. Furthermore, using task-residual functional connectivity and hierarchical clustering, we found that areas in the action observation network and the semantic/default-mode network were functionally connected to these two seed regions, and showed similar representations. Our study provides direct evidence that both networks were concurrently involved in subjective action and emotion understanding. Our approach shows how subjective understanding of action and emotion stimuli can be reliably studied and complement insights based on from predefined stimulus categories.
FAN1 nuclease processes and pauses on disease-associated slipped-DNA repeats: Mechanism against repeat expansions
Authors: Deshmukh Amit Laxmikant , Caron Marie-Christine , Mohiuddin Mohiuddin , Lanni Stella , Panigrahi Gagan B. , Khan Mahreen , Engchuan Worrawat , Shum Natalie , Faruqui Aisha , Wang Peixiang , Yuen Ryan K.C. , Nakamori Masayuki , Nakatani Kazuhiko , Masson Jean-Yves , Pearson Christopher E.
Published: April 2021

FAN1 nuclease is a modifier of repeat expansion diseases, including Huntington’s disease (HD), fragile X syndrome, and autism. The age of HD onset correlates with ongoing ‘inchworm-like’ repeat expansions (1-3 CAG units/event) in HD brains, and is regulated by three modifiers: The first two, repeat tract length and purity exert their effects by enhancing and slowing CAG expansions, respectively, by affecting the formation of slipped-DNAs — mutagenic intermediates of instability; which are processed to expansions by the third modifiers, DNA repair proteins. FAN1 protects against hyper-expansions of repeats, by unknown mechanisms. We show FAN1, through iterative cycles bound, dimerized and cleaved slipped-DNAs, yielding striking patterns of distinctexo-nucleasepausesalong slip-outs; 5′-C↓A↓GC↓A↓G-3′ and 5′-C↓T↓G↓C↓T↓G-3′. The transcriptionally-displaced CAG strand was excised slower than its complementary CTG strand, required A•A and T•T mismatches, as fully-paired hairpinsarrestedexcision progression, while disease-delayingCAAinterruptions further slowed FAN1 excision. In contrast,endo-nucleolytic cleavage was insensitive to slip-outs. Rare FAN1 variants were found in autism individuals with CGG/CCG repeat expansions. Excision of CGG/CCG slip-outs were similarly excised, with CGG being slower than CCG. The slip-out specific ligand, Naphthyridine-Azaquinolone, shown to induce contractions of expanded repeats in cells, required FAN1 for its effect, and protected slip-outs from FAN1’sexo- but notendo-nucleolytic digestion. FAN1’s ‘inchworm’ pausing of slip-out excision is suited to minimize incremental expansions and modulating disease onset.
Analyzing Brain Morphology in Alzheimer’s Disease Using Discriminative and Generative Spiral Networks
Authors: Azcona Emanuel A. , Besson Pierre , Wu Yunan , Kurani Ajay S. , Bandt S. Kathleen , Parrish Todd B. , Katsaggelos Aggelos K. ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: April 2021

Several patterns of atrophy have been identified and strongly related to Alzheimer’s disease (AD) pathology and its progression. Morphological changes in brainshapehave been identified up to ten years before clinical diagnoses of AD, making its early detection more relevant. We propose novel geometric deep learning frameworks for the analysis of brain shape in the context of neurodegeneration caused by AD. Our deep neural networks learn low-dimensional shape descriptors of multiple neuroanatomical structures, instead of handcrafted features for each structure. A discriminative network using spiral convolution on 3D meshes is constructed for thein-vivobinary classification of AD from healthy controls (HCs) using a fast and efficient “spiral” convolution operator on 3D triangular mesh surfaces of human brain subcortical structures extracted from T1-weighted magnetic resonance imaging (MRI). Our network architecture consists of modular learning blocks using residual connections to improve overall classifier performance.

In this work: (1) a discriminative network is used to analyze the efficacy of disease classification using input data from multiple brain structures and compared to using a single hemisphere or a single structure. It also outperforms prior work using spectral graph convolution on the same the same tasks, as well as alternative methods that operate on intermediate point cloud representations of 3D shapes. (2) Additionally, visual interpretations for regions on the surface of brain structures that are associated to true positive AD predictions are generated and fall in accordance with the current reports on the structural localization of pathological changes associated to AD. (3) A conditional generative network is also implemented to analyze the effects of phenotypic priors given to the model (i.e. AD diagnosis) in generating subcortical structures. The generated surface meshes by our model indicate learned morphological differences in the presence of AD that agrees with the current literature on patterns of atrophy associated to the disease. In particular, our inference results demonstrate an overall reduction in subcortical mesh volume and surface area in the presence of AD, especially in the hippocampus. The low-dimensional shape descriptors obtained by our generative model are also evaluated in our discriminative baseline comparisons versus our discriminative network and the alternative shape-based approaches.
TAZ/TEAD complex regulates TGF-β1-mediated fibrosis in iPSC-derived renal organoids
Authors: Yang Xiaoping , Delsante Marco , Daneshpajouhnejad Parnaz , Fenaroli Paride , Mandell Kira Perzel , Wang Xiaoxin , Takahashi Shogo , Halushka Marc K. , Kopp Jeffrey B. , Levi Moshe , Rosenberg Avi Z.
Published: April 2021

Chronic kidney disease (CKD) progresses by replacement of functional tissue compartments with fibrosis, representing a maladaptive repair process. Shifting kidney repair towards a physiologically-intact architecture, rather than fibrosis, is key to blocking CKD progression. In this study, we developed a fibrosis model that uses human induced pluripotent stem cell (iPSC)-based three-dimensional renal organoids, in which exogenous TGF-β1 induces production of extracellular matrix. In these organoids, TGF- β1 increased transcription factor tafazzin (TAZ) expression. Further, in human kidney biopsies, nuclear TAZ expression was markedly increased in mild and moderate fibrosis. In cultured renal tubular cells expressing a fibrogenic program, TAZ formed a trimeric complex with phosphorylated mothers against decapentaplegic homolog 3 (p-SMAD3) and TEA domain protein (TEAD)-4. Overexpression of TEAD4 protein suppressed collagen-1α1 (COL1A1) promoter activity, and expression of TAZ attenuated this inhibition. INT-767, a dual bile acid receptor agonist binding farnesoid X receptor (FXR) and the Takeda G protein-coupled receptor 5 (TGR5), decreased the TGF-β1-induced increase in p-SMAD3 and TAZ, and preserved renal organoid architecture. These data demonstrate, in an iPSC-derived renal organoid fibrosis model, that INT767 prevents fibrosis programs early in the course of tubular injury through modulation of the TEAD4/TAZ pathway.
Asynchronous nuclear cycles in multinucleatedPlasmodium falciparumenable rapid proliferation
Authors: Klaus Severina , Binder Patrick , Kim Juyeop , Machado Marta , Funaya Charlotta , Schaaf Violetta , Klaschka Darius , Kudulyte Aiste , Cyrklaff Marek , Laketa Vibor , Höfer Thomas , Guizetti Julien , Becker Nils B. , Frischknecht Friedrich , Schwarz Ulrich S. , Ganter Markus
Published: April 2021

Malaria-causing parasites proliferate within erythrocytes through schizogony, forming multinucleated stages before cellularization. Nuclear multiplication does not follow a strict geometric 2nprogression and each proliferative cycle produces a heterogeneous number of progeny. Here, by tracking nuclei and DNA replication, we show that individual nuclei replicate their DNA at different times, despite residing in a shared cytoplasm. Extrapolating from experimental data using mathematical modeling, we demonstrate that a limiting factor must exist that slows down the nuclear multiplication rate. Indeed, our data show that temporally overlapping DNA replication events were significantly slower than partially or non-overlapping events. Our findings suggest an evolutionary pressure that selects for asynchronous DNA replication, balancing available resources with rapid pathogen proliferation.
Gas flow permeability and gas pressures in stilt roots of Red Mangrove (Rhizophora mangleL.)
Authors: Searcy Dennis G.
Published: April 2021

The Red Mangrove (Rhizophora mangle) is typically rooted in anoxic mud conditions that require special adaptations for root oxygenation. Each plant has multiple “stilt roots” that descend from upper branches and end in roots buried the mud. In cross section each stilt root consists of a core of porous aerenchyma surrounded by an impermeable layer of xylem, and outside the xylem there is a second layer aerenchyma. Oxygen must be provided to the mud roots through the aerenchyma either by diffusion or by gas flow, where the separate layers could provide up- and down-flow pathways. To test whether the stilt root’s properties were consistent with gas flow, conductivities were measured. A technique was developed that measured flow conductivities in S.I. scientific units without using a flow meter and a calibrated pressure gauge. The core aerenchyma was more permeable to gas flow than any other plant tissue, except for those stems that are hollow tubes. Because there was little lateral leakage from the core aerenchyma, it had pipe-like properties. In the outer aerenchyma gas conductivity was high, and gas flowed easily through large lenticels on the surface of the stilt root. To complete the calculations, gas pressures in the stilt roots were measured. The calculated gas flow rates through mud roots was not sufficient to supply O2for root respiration, suggesting that diffusion may be the more important mechanism for these plants.
The genome of the poecilogonous annelidStreblospio benedicti
Authors: Zakas Christina , Harry Nathan D. , Scholl Elizabeth H. , Rockman Matthew V.
Published: April 2021

Streblospio benedictiis a common marine annelid that has become an important model for developmental evolution. It is the only known example of poecilogony, where two distinct developmental modes occur within a single species, that is due to a heritable difference in egg size. The dimorphic developmental programs and life-histories exhibited in this species depend on differences within the genome, making it an optimal model for understanding the genomic basis of developmental divergence. Studies usingS. benedictihave begun to uncover the genetic and genomic principles that underlie developmental uncoupling, but until now they have been limited by the lack of availability of genomic tools. Here we present an annotated chromosomal-level genome assembly ofS. benedictigenerated from a combination of Illumina reads, Nanopore long reads, Chicago and Hi-C chromatin interaction sequencing, and a genetic map from experimental crosses. At 701.4 Mb, theS. benedictigenome is the largest annelid genome to date that has been assembled to chromosomal scaffolds, yet it does not show evidence of extensive gene family expansion, but rather longer intergenic regions. The complete genome ofS. benedictiis valuable for functional genomic analyses of development and evolution, as well as phylogenetic comparison within the Annelida and the Lophotrochozoa. Despite having two developmental modes, there is no evidence of genome duplication or substantial gene number expansions. Instead, lineage specific repeats account for much of the expansion of this genome compared to other annelids.
Targeting circPTPN12/miR-21-5p/ΔNp63α pathway as a therapeutic strategy for human endometrial fibrosis
Authors: Song Minmin , Zhao Guangfeng , Sun Haixiang , Yao Simin , Zhou Zhenhua , Jiang Peipei , Wu Qianwen , Zhu Hui , Wang Huiyan , Dai Chenyan , Wang Jingmei , Li Ruotian , Cao Yun , lv Haining , Liu Dan , Dai Jianwu , Zhou Yan , Hu Yali
Published: April 2021

Emerging evidence demonstrates the important role of circular RNAs (circRNAs) in regulating pathological processes in various diseases including organ fibrosis. Endometrium fibrosis is the leading cause of uterine infertility, but the role of circRNAs in its pathogenesis is largely unknown. Here, we provide the evidence that upregulation of circPTPN12 in endometrial epithelial cells (EECs) of fibrotic endometrium functions as endogenous sponge of miR-21-5p to inhibit miR-21-5p expression and activity, which in turn results in upregulation of ΔNp63α to induce the epithelial mesenchymal transition (EMT) of EECs (EEC-EMT). In a mouse model of endometrium fibrosis, circPTPN12 appears to be a cofactor of driving EEC-EMT. Our findings reveal the novel mechanism in the pathogenesis of endometrium fibrosis and the potential therapeutic strategy for endometrium fibrosis via targeting circPTPN12/miR-21-5p/ΔNp63α pathway.
The CADM2 gene and behavior: A phenome-wide scan in UK-Biobank
Authors: A. Pasman Joëlle , Chen Zeli , Vink Jacqueline M. , Van Den Oever Michel C. , Pattij Tommy , Vries Taco J. De , Abdellaoui Abdel , Verweij Karin J.H.
Published: April 2021

This phenome-wide association study examined SNP and gene–based associations of the CADM2 gene with 242 psycho-behavioral traits (N=12,211–453,349). We found significant associations with 51 traits, many more than for other genes. We replicated previously reported associations with substance use, risk-taking, and health behavior, and uncovered novel associations with sleep and dietary traits. Accordingly, CADM2 is involved in many psycho-behavioral traits, suggesting a common denominator in their biology.
Changes in eating habits and sedentary behavior during the COVID-19 pandemic in adolescents with chronic conditions
Authors: Mazzolani Bruna Caruso , Smaira Fabiana Infante , Astley Camilla , Iraha Amanda Yuri , Pinto Ana Jessica , Marques Isabela Gouveia , Amarante Milla Cordeiro , Rezende Nathalia Saffioti , Sieczkowska Sofia Mendes , Franco Tathiane Christine , do Amaral Miranda Luana Cristina , Lindoso Lívia , Helito Alberto Carame , Oba Jane , Queiroz Ligia Bruni , R Pereira Rosa Maria , Roschel Hamilton , Silva Clovis Artur , Gualano Bruno
Published: April 2021

Purpose

To report on the impact of the COVID-19 outbreak on eating habits and sedentary behavior among adolescents with multiple chronic conditions (n=347) from a tertiary, referral hospitalvs. healthy peers.

Methods

This observational study was conducted in Sao Paulo (Brazil) between July and October 2020, period in which a set of social distancing measures to contain the pandemic.

Results

The main findings of this study were that adolescents with chronic conditions showed important changes in eating habits (e.g., less often consumption of convenience foods and more often eating in front of television than before quarantine). Also, 86.8% of adolescents with chronic conditions reported increasing screen time during pandemic. No major differences were observed between patients and controls.

Conclusions

Adolescents with chronic conditions exposed to pandemic showed substantial changes in lifestyle, stressing the need for specific care to mitigate poor eating habits and excessive sedentary behavior in this group.
Neuroinvasion and neurotropism by SARS-CoV-2 variants in the K18-hACE2 mouse
Authors: Seehusen Frauke , Clark Jordan J. , Sharma Parul , Bentley Eleanor G , Kirby Adam , Subramaniam Krishanthi , Giuliani Sabina Wunderlin , Hughes Grant L. , Patterson Edward I. , Michael Benedict D. , Owen Andrew , Hiscox Julian A. , Stewart James P. , Kipar Anja
Published: April 2021

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) not only affects the respiratory tract but also causes neurological symptoms such as loss of smell and taste, headache, fatigue or severe cerebrovascular complications. Using transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2) we investigated the spatiotemporal distribution and pathomorphological features in the CNS following intranasal infection with SARS-CoV-2 variants, also after prior influenza A virus infection. Apart from Omicron, we found all variants to frequently spread to and within the CNS. Infection was restricted to neurons and appeared to spread from the olfactory bulb mainly in basally orientated regions in the brain and into the spinal cord, independent of ACE2 expression and without evidence of neuronal cell death, axonal damage or demyelination. However, microglial activation, microgliosis and a mild macrophage and T cell dominated inflammatory response was consistently observed, accompanied by apoptotic death of endothelial, microglial and immune cells, without their apparent infection. Microgliosis and immune cell apoptosis indicate a potential role of microglia for pathogenesis and viral effect in COVID-19 and possible impairment of neurological functions, especially in long COVID. These data may also be informative for the selection of therapeutic candidates, and broadly support investigation of agents with adequate penetration into relevant regions of the CNS.
Quantifying the robustness of the neutron reflectometry technique for structural characterization of polymer brushes
Authors: Gresham Isaac J. , Murdoch Timothy J. , Johnson Edwin C. , Robertson Hayden , Webber Grant B. , Wanless Erica J. , Prescott Stuart W. , Nelson Andrew R. J.
Published: April 2021

Neutron reflectometry is the foremost technique for in situ determination of the volume fraction profiles of polymer brushes at planar interfaces. However, the subtle features in the reflectometry data produced by these diffuse interfaces challenge data interpretation. Historically, data analyses have used least-squares approaches that do not adequately quantify the uncertainty of the modeled profile and ignore the possibility of other structures that also match the collected data (multimodality). Here, a Bayesian statistical approach is used that permits the structural uncertainty and multimodality to be quantified for polymer brush systems. A free-form model is used to describe the volume fraction profile, minimizing assumptions regarding brush structure, while only allowing physically reasonable profiles to be produced. The model allows the total volume of polymer and the profile monotonicity to be constrained. The rigor of the approach is demonstrated via a round-trip analysis of a simulated system, before it is applied to real data examining the well characterized collapse of a thermoresponsive brush. It is shown that, while failure to constrain the interfacial volume and consider multimodality may result in erroneous structures being derived, carefully constraining the model allows for robust determination of polymer brush compositional profiles. This work highlights that an appropriate combination of flexibility and constraint must be used with polymer brush systems to ensure the veracity of the analysis. The code used in this analysis is provided, enabling the reproduction of the results and the application of the method to similar problems.
Crystal structure and Hirshfeld surface analysis of 4,5-dibromo-2-(4-methoxyphenyl)-2,3,4,4a,5,6,7,7a-octahydro-1H-4,6-epoxy-1H-cyclopenta[c]pyridin-1-one
Authors: Mertsalov Dmitriy F. , Surina Nataliya S. , Sorokina Elena A. , Çelikesir Sevim Türktekin , Akkurt Mehmet , Grigoriev Mikhail S. , Mlowe Sixberth
Published: April 2021

The molecule of the title compound, C15H15Br2NO3, comprises a fused tricyclic system consisting of two five-membered rings (cyclopentane and tetrahydrofuran) and one six-membered ring (tetrahydropyridinone). Both five-membered rings of the tricyclic system have envelope conformations, and the conformation of the six-membered cycle is intermediate between chair and half-chair. In the crystal, the molecules are linked by C—H...O hydrogen bonds and C—H...π, C—Br...π and C...O interactions into double layers. The layers are connected into a three-dimensional network by van der Waals interactions.
β‐Glycyrrhetinic acid inhibits the bacterial growth and biofilm formation by supragingival plaque commensals
Authors: Dewake Nanae , Ma Xiangtao , Sato Kayo , Nakatsu Susumu , Yoshimura Kenji , Eshita Yoshiyuki , Fujinaka Hidetake , Yano Yoshitaka , Yoshinari Nobuo , Yoshida Akihiro
Published: April 2021

β‐Glycyrrhetinic acid (BGA) is a natural antibacterial agent. Previous studies reported that BGA has antibacterial effects against several bacteria. This study evaluated the effects of BGA on the regulation of supragingival plaque bacteria. First, the minimum inhibitory concentrations (MICs) of BGA against oral bacteria were measured. Next, the minimum concentrations for inhibition of biofilm formation were evaluated against Streptococcus mutans and Streptococcus sobrinus, possessing insoluble glucan synthesis abilities. The MICs of biofilm formation by these bacteria ranged from 1/8 to 2× MIC. Furthermore, the inhibition effects of BGA against the coaggregation of Porphyromonas gingivalis and Streptococcus gordonii were evaluated. BGA at 32 or 64 μg/mL inhibited the coaggregation of these bacteria after a 30 min incubation. Lastly, the inhibition effects of BGA against human supragingival plaque bacteria were evaluated. Human supragingival plaque samples were obtained from 12 healthy donors. The inhibition effects of BGA against biofilm formation by these plaque bacteria were evaluated. Of 12 samples, the biofilm formation by 11 was significantly attenuated by 128–256 μg/mL of BGA. The number of colony forming units in these biofilms was also significantly attenuated. In conclusion, it was revealed that BGA inhibits the growth and biofilm formation of bacteria, furthermore, the same effect was confirmed with supragingival plaque bacteria. BGA is a good candidate for a natural agent that prevents the outbreak and progression of periodontal disease because it suppresses not only the growth and biofilm formation of bacteria, but also the coaggregation of P. gingivalis with plaque bacteria.
A novel non‐invasive identification of genome editing mutants from insect exuviae
Authors: Wang Xiao‐Xiao , Li Jing , Wang Tong‐Xin , Yang Yi‐Nuo , Zhang Hai‐Kang , Zhou Meng , Kang Le , Wei Li‐Ya
Published: April 2021

With the wide application of genome editing in insects, a simple and efficient identification method is urgently needed to meet the increasing demand for mutation detection. Here, taking migratory locusts as a model system, we developed a non‐invasive method to accurately identify genome‐edited mutants by using DNA from insect exuviae. We compared the quantity and quality of genomic DNA from exuviae in five instar hoppers and found that the 1st instar exuviae had the highest DNA yield and content, while the 3rd instar exuviae had the best quality. Consensus genotypes were identified from genomic DNA of hoppers at different developmental stages in the same individuals. Moreover, we demonstrated that the amplification products from DNA extracted from locust exuviae are the consensus sequences with those from the hemolymph and foreleg pre‐tarsus. Therefore, non‐invasive samples provide the same genotyping results as minimally invasive and invasive samples of the same individuals. Furthermore, this identification method that uses genomic DNA from exuviae can be used for early screening of positive genome‐edited individuals in each generation for adult crossing. In our study, the non‐invasive identification method was not only simpler and provided results earlier than existing methods, but also had a better reproducibility and accuracy. This non‐invasive identification approach using genomic DNA from exuviae can be adapted to meet the growing demand for genetic analysis and will find wide application in insect genome editing research.
Primär kutane T‐Zell‐Lymphome im Kindes‐ und Jugendalter
Authors: Wohlmuth‐Wieser Iris
Published: April 2021

Primär kutane Lymphome sind extranodale T‐ oder B‐Zell‐Non‐Hodgkin‐Lymphome, die vorwiegend ältere Patienten betreffen, aber in allen Altersgruppen einschließlich der ersten Lebensjahre auftreten können. Die Diagnose kutaner Lymphome ist eine Herausforderung und erfordert einen hohen klinischen Verdacht sowie enge Zusammenarbeit zwischen Dermatologen, pädiatrischen Onkologen und Pathologen. Generell müssen primär kutane Lymphome von sekundär kutanen Lymphomen, welche meist von nodalen oder extranodalen Lymphomen ausgehen, unterschieden werden. Die häufigsten primär kutanen Lymphome im Kindesalter sind T‐Zell Lymphome, wobei Mycosis fungoides das häufigste kutane T‐Zell‐Lymphom darstellt, gefolgt von CD30+ lymphoproliferativen Erkrankungen. Während klinisch‐pathologische Merkmale kutaner Lymphome bei Jugendlichen und Erwachsenen ähnlich sind, gibt es wichtige Unterschiede bezüglich klinischer Präsentation, Diagnose und Behandlung. Die hypopigmentierte Variante der Mycosis fungoides scheint in der pädiatrischen Altersgruppe überrepräsentiert zu sein. Prognose und Behandlung der Mycosis fungoides sind stadienabhängig. Die Mehrheit der Kinder weist ein frühes Krankheitsstadium auf und spricht gut auf topische Kortikosteroide und Phototherapie an.
Liver macrophages and inflammation in physiology and physiopathology of non‐alcoholic fatty liver disease
Authors: Thibaut Ronan , Gage Matthew C. , Pineda‐Torra Inès , Chabrier Gwladys , Venteclef Nicolas , Alzaid Fawaz
Published: April 2021

Non‐alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome, being a common comorbidity of type 2 diabetes and with important links to inflammation and insulin resistance. NAFLD represents a spectrum of liver conditions ranging from steatosis in the form of ectopic lipid storage, to inflammation and fibrosis in nonalcoholic steatohepatitis (NASH). Macrophages that populate the liver play important roles in maintaining liver homeostasis under normal physiology and in promoting inflammation and mediating fibrosis in the progression of NAFLD toward to NASH. Liver macrophages are a heterogenous group of innate immune cells, originating from the yolk sac or from circulating monocytes, that are required to maintain immune tolerance while being exposed portal and pancreatic blood flow rich in nutrients and hormones. Yet, liver macrophages retain a limited capacity to raise the alarm in response to danger signals. We now know that macrophages in the liver play both inflammatory and noninflammatory roles throughout the progression of NAFLD. Macrophage responses are mediated first at the level of cell surface receptors that integrate environmental stimuli, signals are transduced through multiple levels of regulation in the cell, and specific transcriptional programmes dictate effector functions. These effector functions play paramount roles in determining the course of disease in NAFLD and even more so in the progression towards NASH. The current review covers recent reports in the physiological and pathophysiological roles of liver macrophages in NAFLD. We emphasise the responses of liver macrophages to insulin resistance and the transcriptional machinery that dictates liver macrophage function.
Effectiveness of a video‐based advance care planning intervention in hospitalized elderly patients: A randomized controlled trial
Authors: Lin Li‐Hwa , Cheng Hui‐Chuan , Chen Yu‐Chih , Chien Li‐Yin
Published: April 2021

Aim

This study aimed to develop a video‐based advance care planning intervention, and examine the effectiveness of the intervention on knowledge, behavioral intentions and advance directive signing among older patients admitted to a geriatric unit in Taiwan.

Methods

This randomized controlled trial was carried out in two geriatric wards of a medical center in northern Taiwan, between June 2014 and June 2015. The participants were randomly assigned to the intervention (n = 39) or control (n = 43) group. Participants in the intervention group watched a 5‐min video regarding advance care planning. The control group received usual care. Structured questionnaires on advance care planning knowledge and behavioral intentions were administered to both groups before and after the intervention. Advance directive signing was carried out until 2 weeks after hospital discharge through a chart review.

Results

The intervention group showed a significantly higher advance care planning knowledge score and behavioral intention score than the control group post‐intervention. The rate of advance directive signing was 33.3% in the intervention group and 9.3% in the control group (P = 0.01).

Conclusions

This study showed the effectiveness of video‐based interventions in increasing advance care planning knowledge, behavioral intention and advance directive signing among hospitalized older patients. Geriatric wards could use our model to promote advance care planning among older patients. Geriatr Gerontol Int 2021; 21: 478–484.
Comparison of stereotactic body radiotherapy and radiofrequency ablation for hepatocellular carcinoma: Systematic review and meta‐analysis of propensity score studies
Authors: Eriguchi Takahisa , Takeda Atsuya , Tateishi Yudai , Tsurugai Yuichiro , Sanuki Naoko , Ebinuma Hirotoshi , Horita Nobuyuki
Published: April 2021

Aim

Stereotactic body radiotherapy (SBRT) is an emerging treatment for hepatocellular carcinoma (HCC) and has shown excellent local control (LC), as has radiofrequency ablation (RFA). As no randomized controlled trial has compared SBRT and RFA for HCC, data from a propensity score matched study (PSMS) are valuable. However, the results varied greatly and depended on composing factors of Barcelona Clinic Liver Cancer staging (BCLC‐factors) adjusted. Therefore, we undertook a systematic review and meta‐analyses of the studies focusing on BCLC‐factors matching.

Methods

We systematically searched PubMed, the Cochrane database, EMBASE, and Web of Science to identify studies comparing RFA and SBRT using propensity scores. The hazard ratios (HRs) of overall survival (OS) and LC from BCLC‐factor‐matched and ‐unmatched PSMS were pooled. Heterogeneity between the data from these studies was assessed.

Results

Three BCLC‐factor‐matched studies were identified. Stereotactic body radiotherapy led to comparable OS (HR, 0.89; 95% CI, 0.74–1.08; p = 0.24; I2 = 0%; p for heterogeneity, 0.56) and significantly better LC (HR, 0.39; 95% CI, 0.30–0.51; p < 0.001; I2 = 0%; p for heterogeneity, 0.67). We also identified three additional BCLC‐factor‐unmatched studies (HR of OS, 1.41; 95% CI, 1.21–1.65; p < 0.0001; I2 = 0%; p for heterogeneity, 0.63). However, considerable heterogeneity was observed for HR of OS between BCLC‐factor‐matched and ‐unmatched studies (I2 = 92.6%; p for heterogeneity, 0.0002).

Conclusions

When BCLC‐factors were properly adjusted, the results of the meta‐analysis revealed equivalent OS and better LC for SBRT compared with RFA. Stereotactic body radiotherapy could be an alternative treatment option for HCC.