Amphicarpy (seed heteromorphy) is a unique and fascinating reproductive strategy wherein a single plant produces both aerial and subterranean fruits. This strategy is believed to be an adaptation to life under stressful or uncertain environments. Here, we sequenced and de novo assembled a chromosome-level genome assembly of the legume Amphicarpaea edgeworthii Benth. The 299-Mb A. edgeworthii genome encodes 27 899 protein-coding genes and is the most compact sequenced legume genome reported until date. Its reduced genome size may be attributed to the reduced long-terminal repeat retrotransposon content, which stems from the unequal homologous recombination. Gene families related to immunity and stress resistance have been contracted in A. edgeworthii, which is consistent with the notion that the amphicarpic reproductive strategy may be a complementary mechanism for its weak environmental-adaptation ability. We demonstrated the 'ABCE' model for the differentiation of chasmogamous and cleistogamous flowers. In addition, the characteristics of aerial and subterranean seeds in hard-seededness were explored. Thus, we suggest that the A. edgeworthii genome, which is the first of an amphicarpic plant, offers significant insights into its unusual reproductive strategy that is a key resource towards comprehending the evolution of angiosperms.

Previous reports indicated that the Slit2-Robo signalling pathway is involved in embryonic heart development and fibrosis in other solid organs, but its function in adult cardiac fibrosis has not been investigated. Here, we investigate the role of the Slit2-Robo1 signalling pathway in cardiac fibrosis.

To investigate the association between CT imaging features and survival outcomes in patients with primary invasive mucinous adenocarcinoma (IMA).

Dysgeusia is the first recognized oral symptom of novel coronavirus disease (COVID-19). In this review article, we described oral lesions of COVID-19 patients. We searched PubMed library and Google Scholar for published literature since December 2019 until September 2020. Finally, we selected 35 articles including case reports, case series and letters to editor. Oral manifestations included ulcer, erosion, bulla, vesicle, pustule, fissured or depapillated tongue, macule, papule, plaque, pigmentation, halitosis, whitish areas, hemorrhagic crust, necrosis, petechiae, swelling, erythema, and spontaneous bleeding. The most common sites of involvement in descending order were tongue (38%), labial mucosa (26%), and palate (22%). Suggested diagnoses of the lesions were aphthous stomatitis, herpetiform lesions, candidiasis, vasculitis, Kawasaki-like, EM-like, mucositis, drug eruption, necrotizing periodontal disease, angina bullosa-like, angular cheilitis, atypical Sweet syndrome, and Melkerson-Rosenthal syndrome. Oral lesions were symptomatic in 68% of the cases. Oral lesions were nearly equal in both genders (49% female and 51% male). Patients with older age and higher severity of COVID-19 disease had more widespread and sever oral lesions. Lack of oral hygiene, opportunistic infections, stress, immunosuppression, vasculitis, and hyper-inflammatory response secondary to COVID-19 are the most important predisposing factors for onset of oral lesions in COVID-19 patients.

This study in Burkina Faso investigated whether offspring of young mothers who had received weekly periconceptional iron supplementation in a randomised controlled trial were at increased risk of malaria. A child safety survey was undertaken in the peak month of malaria transmission towards the end of the trial to assess child iron biomarkers, nutritional status, anaemia and malaria outcomes. Antenatal iron biomarkers, preterm birth, fetal growth restriction and placental pathology for malaria and chorioamnionitis were assessed. Data were available for 180 babies surviving to the time of the survey when their median age was 9 months. Prevalence of maternal iron deficiency in the last trimester based on low body iron stores was 16%. Prevalence of active placental malaria infection was 24.8%, past infection 59% and chorioamnionitis 55.6%. Babies of iron supplemented women had lower median gestational age. Four out of five children ≥ 6 months were iron deficient, and 98% were anaemic. At 4 months malaria prevalence was 45%. Child iron biomarkers, anaemia and malaria outcomes did not differ by trial arm. Factors associated with childhood parasitaemia were third trimester C-reactive protein level (OR 2.1; 95% CI 1.1-3.9), active placental malaria (OR 5.8; 1.0-32.5, P = 0.042) and child body iron stores (OR 1.13; 1.04-1.23, P = 0.002). Chorioamnionitis was associated with reduced risk of child parasitaemia (OR 0.4; 0.1-1.0, P = 0.038). Periconceptional iron supplementation of young women did not alter body iron stores of their children. Higher child body iron stores and placental malaria increased risk of childhood parasitaemia.

The objective was to systematically review monetary data related to management of incontinence-associated dermatitis (IAD) in an adult population. Six electronic databases were searched: MEDLINE, CINAHL, Web of Science, EMBASE, The Cochrane Library and EconLit. The search string combined index terms and text words related to IAD and monetary data. The quality of the articles was assessed using the consensus on Health Economic Criteria. Results were synthesised narratively because of methodological heterogeneity. Nine studies were included. Only direct medical costs were reported. The product cost per application for prevention ranged between $0.05 and $0.52, and for treatment between $0.20 and $0.35. The product cost per patient/day for prevention ranged between $0.23 and $20.17. The product cost of IAD prevention and treatment per patient/day ranged between $0.57 and $1.08. The cost to treat IAD did not consider the treatment of secondary infection. The calculation of labour cost and total cost differed considerably between studies. Summarising monetary data is a challenge because of heterogeneity in currencies, settings, samples, time horizons, health- and cost outcome valuation, IAD definition and measurements, and included costs. Procedures for health economic evaluations are to be clarified to guarantee valid interpretation and comparison with other studies.

Randomised controlled trials of therapeutic interventions for pressure injuries should include a clear description of outcomes to increase transparency and replicability and improve the construction of scientific evidence. The objective of this study was to assess the completeness of the descriptions of the outcomes of therapeutic interventions in adults with pressure injury (PI) and factors associated with completeness. This was a systematic methodological survey. The completeness of the outcome was assessed according to five criteria: domain (title), specific measure (technique/instrument used), specific metric, or format of the outcome data of each participant that was used for analysis, aggregation (method data from each group were summarised), and time that was used for analysis. Sixty-eight studies were included for analysis. A total of 265 outcomes were reported, and 46 trials (67.6%) had 73 primary outcomes, which were mainly intermediates/substitutes (78.8%). The main outcome evaluated was the ulcer area reduction (36.6%). Approximately 37.2% of the outcomes were incompletely reported, and the least described element was the data aggregation method (72.8%). Only 48.4% of the outcomes with the specified technique had the same reference or validation. Poor quality of reporting outcomes was associated with studies with an older year of publication and a small sample size, single-center studies, and those sponsored by industry. PI studies use many outcomes, mostly surrogates or intermediates, and some of them are incompletely described.

The aim of the UniProt Knowledgebase is to provide users with a comprehensive, high-quality and freely accessible set of protein sequences annotated with functional information. In this article, we describe significant updates that we have made over the last two years to the resource. The number of sequences in UniProtKB has risen to approximately 190 million, despite continued work to reduce sequence redundancy at the proteome level. We have adopted new methods of assessing proteome completeness and quality. We continue to extract detailed annotations from the literature to add to reviewed entries and supplement these in unreviewed entries with annotations provided by automated systems such as the newly implemented Association-Rule-Based Annotator (ARBA). We have developed a credit-based publication submission interface to allow the community to contribute publications and annotations to UniProt entries. We describe how UniProtKB responded to the COVID-19 pandemic through expert curation of relevant entries that were rapidly made available to the research community through a dedicated portal. UniProt resources are available under a CC-BY (4.0) license via the web at https://www.uniprot.org/.

Comparative genomics is the analysis of genomic relationships among different species and serves as a significant base for evolutionary and functional genomic studies. GreenPhylDB (https://www.greenphyl.org) is a database designed to facilitate the exploration of gene families and homologous relationships among plant genomes, including staple crops critically important for global food security. GreenPhylDB is available since 2007, after the release of the Arabidopsis thaliana and Oryza sativa genomes and has undergone multiple releases. With the number of plant genomes currently available, it becomes challenging to select a single reference for comparative genomics studies but there is still a lack of databases taking advantage several genomes by species for orthology detection. GreenPhylDBv5 introduces the concept of comparative pangenomics by harnessing multiple genome sequences by species. We created 19 pangenes and processed them with other species still relying on one genome. In total, 46 plant species were considered to build gene families and predict their homologous relationships through phylogenetic-based analyses. In addition, since the previous publication, we rejuvenated the website and included a new set of original tools including protein-domain combination, tree topologies searches and a section for users to store their own results in order to support community curation efforts.

Intrauterine adhesions (IUAs), the leading cause of uterine infertility, are characterized by endometrial fibrosis. The management of IUA is challenging because the pathogenesis of the disease largely unknown. In this study, we demonstrate that the mRNA and protein levels of high mobility group AT-hook 2 (HMGA2) were increased by nearly 3-fold (P < 0.0001) and 5-fold (P = 0.0095) in the endometrial epithelial cells (EECs) of IUA patients (n = 18) compared to controls. In vivo and in vitro models of endometrial fibrosis also confirmed the overexpression of HMGA2 in EECs. In vitro cell experiments indicated that overexpression of HMGA2 promoted the epithelial-mesenchymal transition (EMT) while knockdown of HMGA2 reversed transforming growth factor-β-induced EMT. A dual luciferase assay confirmed let-7d microRNA downregulated HMGA2 and repressed the pro-EMT effect of HMGA2 in vitro and in vivo. Therefore, our data reveal that HMGA2 promotes IUA formation and suggest that let-7d can depress HMGA2 and may be a clinical targeting strategy in IUA.

The MobiDB database (URL: https://mobidb.org/) provides predictions and annotations for intrinsically disordered proteins. Here, we report recent developments implemented in MobiDB version 4, regarding the database format, with novel types of annotations and an improved update process. The new website includes a re-designed user interface, a more effective search engine and advanced API for programmatic access. The new database schema gives more flexibility for the users, as well as simplifying the maintenance and updates. In addition, the new entry page provides more visualisation tools including customizable feature viewer and graphs of the residue contact maps. MobiDB v4 annotates the binding modes of disordered proteins, whether they undergo disorder-to-order transitions or remain disordered in the bound state. In addition, disordered regions undergoing liquid-liquid phase separation or post-translational modifications are defined. The integrated information is presented in a simplified interface, which enables faster searches and allows large customized datasets to be downloaded in TSV, Fasta or JSON formats. An alternative advanced interface allows users to drill deeper into features of interest. A new statistics page provides information at database and proteome levels. The new MobiDB version presents state-of-the-art knowledge on disordered proteins and improves data accessibility for both computational and experimental users.

The protein cloud-point temperature (TCloud) is a known representative of protein-protein interaction strength and provides valuable information during the development and characterization of protein-based products, such as biopharmaceutics. A high-throughput low volume TCloud detection method was introduced in preceding work, where it was concluded that the extracted value is an apparent TCloud (TCloud,app). As an understanding of the apparent nature is imperative to facilitate inter-study data comparability, the current work was performed to systematically evaluate the influence of 3 image analysis strategies and 2 experimental parameters (sample volume and cooling rate) on TCloud,app detection of lysozyme. Different image analysis strategies showed that TCloud,app is detectable by means of total pixel intensity difference and the total number of white pixels, but the latter is also able to extract the ice nucleation temperature. Experimental parameter variation showed a TCloud,app depression for increasing cooling rates (0.1-0.5 °C/min), and larger sample volumes (5-24 μL). Exploratory thermographic data indicated this resulted from a temperature discrepancy between the measured temperature by the cryogenic device and the actual sample temperature. Literature validation confirmed that the discrepancy does not affect the relative inter-study comparability of the samples, regardless of the image analysis strategy or experimental parameters. Additionally, high measurement precision was demonstrated, as TCloud,app changes were detectable down to a sample volume of only 5 μL and for 0.1 °C/min cooling rate increments. This work explains the apparent nature of the TCloud detection method, showcases its detection precision, and broadens the applicability of the experimental setup.

Three dimensional (3D) organ-like (organotypic) culture models are a rapidly advancing area of in vitro biological science. In contrast to monolayer cell culture methods which were developed to achieve proliferation of animal cells in the beginning of in vitro biology, the advancements in 3D culture methods are designed to promote cellular differentiation, and to achieve in vivo-like 3D structure and organotypic functions. This project was conceived through the Society for In Vitro Biology to draw on the expertise of individual scientists with special expertise in organotypic cultures of selected tissues or associated interrogation methods to prepare individual-focused reviews in this series. This introductory manuscript will review the early achievements of animal cell culture in monolayer culture and the limitations of that approach to reproduce functioning organ systems. Among these are the nature and 3D architecture of the substrate on which or in which the cells are grown, physical and mechanical clues from the substrate, cell-cell interactions, and defined biochemical factors that trigger the induction of the 3D organotypic differentiation. The organoid culture requires a source of cells with proliferative capacity (ranging from tissue-derived stem or immortalized cells to the iPSC cultures), a suitable substrate or matrix with the mechanical and stimulatory properties appropriate for the organotypic construct and the necessary stimulation of the culture to drive differentiation of the cell population to form the functioning organotypic construct. Details for each type of organotypic construct will be provided in the following papers.

We discuss the evidence on the occurrence of de novo seizures in patients with COVID-19, the consequences of this catastrophic disease in people with epilepsy (PWE), and the electroencephalographic (EEG) findings in patients with COVID-19.

A major limitation of total knee replacement (TKR), as with other joint replacements, is the risk of revision. Revision TKR is associated with high risk and economic burden to patients, healthcare providers, and societies. It will be worthwhile to assess the economic burden of revision TKR across countries or different study settings. This study aims to review the literature on the cost of revision TKR to assess costs across countries and studies, estimate a pooled cost estimate for homogenous data, and identify major cost components that contribute to the cost burden.

The electrogenic Na+ /HCO3- cotransporter NBCe1-B is widely expressed in many tissues, including pancreas, submandibular gland, brain, heart, etc. NBCe1-B has very low activity under basal condition due to auto-inhibition, but can be fully activated by protein interaction with the IP3R-binding protein released with inositol 1,4,5-trisphosphate (IRBIT). The structural components of the auto-inhibition domain and the IRBIT-binding domain of NBCe1-B are finely characterized based on systematic mutations in the present study and data from previous studies. Reducing negative charges on the cytosol side of the transmembrane domain greatly decreases the magnitude of the auto-inhibition of NBCe1-B. We propose that the auto-inhibition domain functions as a brake module that inactivates NBCe1-B by binding to, via electrostatic attraction, the transmembrane domain; IRBIT activates NBCe1-B by releasing the brake from the transmembrane domain via competitive binding to the auto-inhibition domain.

Most of the fascinating phenomena studied in cell biology emerge from interactions among highly organized multimolecular structures embedded into complex and frequently dynamic cellular morphologies. For the exploration of such systems, computer simulation has proved to be an invaluable tool, and many researchers in this field have developed sophisticated computational models for application to specific cell biological questions. However, it is often difficult to reconcile conflicting computational results that use different approaches to describe the same phenomenon. To address this issue systematically, we have defined a series of computational test cases ranging from very simple to moderately complex, varying key features of dimensionality, reaction type, reaction speed, crowding, and cell size. We then quantified how explicit spatial and/or stochastic implementations alter outcomes, even when all methods use the same reaction network, rates, and concentrations. For simple cases, we generally find minor differences in solutions of the same problem. However, we observe increasing discordance as the effects of localization, dimensionality reduction, and irreversible enzymatic reactions are combined. We discuss the strengths and limitations of commonly used computational approaches for exploring cell biological questions and provide a framework for decision making by researchers developing new models. As computational power and speed continue to increase at a remarkable rate, the dream of a fully comprehensive computational model of a living cell may be drawing closer to reality, but our analysis demonstrates that it will be crucial to evaluate the accuracy of such models critically and systematically.

Studies have shown that there is a high correlation between atopic dermatitis and decrease in ceramide content in the lipid bilayer of skin. Moreover, it has been shown that the reduction in ceramide content in the stratum corneum is unique to atopic dermatitis, indicating that there are particular structural differences between the lipid bilayers of normal and atopic skin.

The queen-worker caste system of eusocial insects represents a prime example of developmental polyphenism (environmentally-induced phenotypic polymorphism) and is intrinsic to the evolution of advanced eusociality. However, the comparative molecular basis of larval caste determination and subsequent differentiation in the eusocial Hymenoptera remains poorly known. To address this issue within bees, we profiled caste-associated gene expression in female larvae of the intermediately eusocial bumblebee Bombus terrestris. In B. terrestris, female larvae experience a queen-dependent period during which their caste fate as adults is determined followed by a nutrition-sensitive period also potentially affecting caste fate but for which the evidence is weaker. We used mRNA-seq and qRT-PCR validation to isolate genes differentially expressed between each caste pathway in larvae at developmental stages before and after each of these periods. We show that differences in gene expression between caste pathways are small in totipotent larvae, then peak after the queen-dependent period. Relatively few novel (i.e., taxonomically-restricted) genes were differentially expressed between castes, though novel genes were significantly enriched in late-instar larvae in the worker pathway. We compared sets of caste-associated genes in B. terrestris with those reported from the advanced eusocial honeybee, Apis mellifera, and found significant but relatively low levels of overlap of gene lists between the two species. These results suggest both the existence of low numbers of shared toolkit genes and substantial divergence in caste-associated genes between Bombus and the advanced eusocial Apis since their last common eusocial ancestor.

While antibiotics are intended to specifically target bacteria, most are known to affect host cell physiology. In addition, some antibiotic classes are reported as immunosuppressive for reasons that remain unclear. Here, we show that Linezolid, a ribosomal-targeting antibiotic (RAbo), effectively blocked the course of a T cell-mediated autoimmune disease. Linezolid and other RAbos were strong inhibitors of T helper-17 cell effector function in vitro, showing that this effect was independent of their antibiotic activity. Perturbing mitochondrial translation in differentiating T cells, either with RAbos or through the inhibition of mitochondrial elongation factor G1 (mEF-G1) progressively compromised the integrity of the electron transport chain. Ultimately, this led to deficient oxidative phosphorylation, diminishing nicotinamide adenine dinucleotide concentrations and impairing cytokine production in differentiating T cells. In accordance, mice lacking mEF-G1 in T cells were protected from experimental autoimmune encephalomyelitis, demonstrating that this pathway is crucial in maintaining T cell function and pathogenicity.