title: PeerJ description: Articles published in PeerJ link: https://peerj.com/articles/index.rss3?journal=peerj&page=919 creator: info@peerj.com PeerJ errorsTo: info@peerj.com PeerJ language: en title: Mycophenolate suppresses inflammation by inhibiting prostaglandin synthases: a study of molecular and experimental drug repurposing link: https://peerj.com/articles/11360 last-modified: 2021-04-30 description: Mycophenolate mofetil is an established anti-proliferative and immune-suppressive agent that minimizes the proliferation of inflammatory cells by interfering with nucleic acid synthesis. Herein, we report our discovery of the prostaglandin inhibiting properties of MMF, which offers new applications for the drug in the treatment of inflammatory diseases. The estimated values of IC50MMFCOX-1, IC50MMFCOX-2, and IC50MMF5-LOX were 5.53, 0.19, and 4.47 µM, respectively. In contrast, mycophenolic acid (MPA) showed slightly stronger inhibition: IC50MPACOX-1, IC50MPACOX-2, and IC50MPA5-LOX were 4.62, 0.14, and 4.49 µM, respectively. These results indicate that MMF and MPA are, respectively, 28.6 and 33 times more selective for cyclooxygenase-2 than for cyclooxygenase-1, which implies that MMF would have less impact on the gastric mucosa than most nonselective, nonsteroidal anti-inflammatory drugs. Furthermore, MMF provided dose-dependent relief of acute inflammation in the carrageenan-induced rat paw edema test, with results comparable to those of celecoxib and indomethacin. Molecular dynamics simulations indicated that the MMF bond with COX-2 was stable, as evidenced by a low root-mean-square deviation of atomic positions, complementary per-residue root-mean-square fluctuation, and 0–4 hydrogen bonds during the 50-ns simulation time. Therefore, MMF provides immune-suppressing, cyclooxygenase-inhibiting, and inflammation-relieving properties. Our results indicate that MMF can be 1) repositioned for inflammation treatment without the need for further expensive clinical trials, 2) used for local acute inflammations, and 3) used as a sparing agent for other steroid and non-steroid anti-inflammatory medications, especially in topical applications. creator: Fahad Al-Hizab creator: Mahmoud Kandeel uri: https://doi.org/10.7717/peerj.11360 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2021 Al-Hizab and Kandeel title: The hypoferremic response to acute inflammation is maintained in thalassemia mice even under parenteral iron loading link: https://peerj.com/articles/11367 last-modified: 2021-04-30 description: BackgroundHepcidin controls iron homeostasis by inducing the degradation of the iron efflux protein, ferroportin (FPN1), and subsequently reducing serum iron levels. Hepcidin expression is influenced by multiple factors, including iron stores, ineffective erythropoiesis, and inflammation. However, the interactions between these factors under thalassemic condition remain unclear. This study aimed to determine the hypoferremic and transcriptional responses of iron homeostasis to acute inflammatory induction by lipopolysaccharide (LPS) in thalassemic (Hbbth3/+) mice with/without parenteral iron loading with iron dextran.MethodsWild type and Hbbth3/+ mice were intramuscularly injected with 5 mg of iron dextran once daily for two consecutive days. After a 2-week equilibration, acute inflammation was induced by an intraperitoneal injection of a single dose of 1 µg/g body weight of LPS. Control groups for both iron loading and acute inflammation received equal volume(s) of saline solution. Blood and tissue samples were collected at 6 hours after LPS (or saline) injection. Iron parameters and mRNA expression of hepcidin as well as genes involved in iron transport and metabolism in wild type and Hbbth3/+ mice were analyzed and compared by Kruskal–Wallis test with pairwise Mann–Whitney U test.ResultsWe found the inductive effects of LPS on liver IL-6 mRNA expression to be more pronounced under parenteral iron loading. Upon LPS administration, splenic erythroferrone (ERFE) mRNA levels were reduced only in iron-treated mice, whereas, liver bone morphogenetic protein 6 (BMP6) mRNA levels were decreased under both control and parenteral iron loading conditions. Despite the altered expression of the aforementioned hepcidin regulators, the stimulatory effect of LPS on hepcidin mRNA expression was blunt in iron-treated Hbbth3/+ mice. Contrary to the blunted hepcidin response, LPS treatment suppressed FPN1 mRNA expression in the liver, spleen, and duodenum, as well as reduced serum iron levels of Hbbth3/+ mice with parenteral iron loading.ConclusionOur study suggests that a hypoferremic response to LPS-induced acute inflammation is maintained in thalassemic mice with parenteral iron loading in a hepcidin-independent manner. creator: Chanita Sanyear creator: Buraporn Chiawtada creator: Punnee Butthep creator: Saovaros Svasti creator: Suthat Fucharoen creator: Patarabutr Masaratana uri: https://doi.org/10.7717/peerj.11367 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2021 Sanyear et al. title: Genome-wide identification and expression analysis of the trehalose-6-phosphate synthase (TPS) gene family in cucumber (Cucumis sativus L.) link: https://peerj.com/articles/11398 last-modified: 2021-04-30 description: Trehalose-6-phosphate synthase (TPS) is significant in the growth, development and stress resistance of plants. We identified the cucumber TPS family and its physicochemical properties, domains, gene structures, evolutionary relationships, gene locations, cis-acting elements, conserved motifs, and expression patterns using bioinformatics. Our results uncovered seven CsTPS genes in the cucumber genome and named CsTPS1–CsTPS7 according to their locations in the chromosomes. Seven CsTPS genes were randomly distributed in six cucumber chromosomes. Domain analysis showed that the TPS and TPP domains exist in all CsTPSs, and an additional hydrolase-3 domain exist in CsTPS3, CsTPS5 and CsTPS6. Phylogenetic analysis showed that TPS proteins from Arabidopsis, rice, soybean, and cucumber were divided into two subfamilies (Class I and Class II) and they were further divided into seven subgroups. TPS proteins from Arabidopsis and cucumber were grouped together, suggesting a close evolutionary relationship. Gene structure analysis indicated that most Class I genes contained 16–17 introns, while Class II genes (except CsTPS7) had two introns. Motif analysis showed that Class II genes had 10 complete conserved motifs, while Class I genes lacked motif 8 and motif 9. Furthermore, CsTPS genes possessed numerous cis-acting elements related to stress, hormone, and light response in the promoter regions. GO analysis indicated multiple functions for the CsTPS proteins. Expression analysis of CsTPS genes in different tissues found that they were expressed in roots, stems and leaves, with the highest expression levels in roots. The expression analysis of CsTPSs under different treatments showed that CsTPS genes may participate in the response to abiotic stress, plant hormones and sugar treatments. creator: Yuanyuan Dan creator: Yuan Niu creator: Chunlei Wang creator: Mei Yan creator: Weibiao Liao uri: https://doi.org/10.7717/peerj.11398 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2021 Dan et al. title: PhyloPrimer: a taxon-specific oligonucleotide design platform link: https://peerj.com/articles/11120 last-modified: 2021-04-29 description: Many environmental and biomedical biomonitoring and detection studies aim to explore the presence of specific organisms or gene functionalities in microbiome samples. In such cases, when the study hypotheses can be answered with the exploration of a small number of genes, a targeted PCR-approach is appropriate. However, due to the complexity of environmental microbial communities, the design of specific primers is challenging and can lead to non-specific results. We designed PhyloPrimer, the first user-friendly platform to semi-automate the design of taxon-specific oligos (i.e., PCR primers) for a gene of interest. The main strength of PhyloPrimer is the ability to retrieve and align GenBank gene sequences matching the user’s input, and to explore their relationships through an online dynamic tree. PhyloPrimer then designs oligos specific to the gene sequences selected from the tree and uses the tree non-selected sequences to look for and maximize oligo differences between targeted and non-targeted sequences, therefore increasing oligo taxon-specificity (positive/negative consensus approach). Designed oligos are then checked for the presence of secondary structure with the nearest-neighbor (NN) calculation and the presence of off-target matches with in silico PCR tests, also processing oligos with degenerate bases. Whilst the main function of PhyloPrimer is the design of taxon-specific oligos (down to the species level), the software can also be used for designing oligos to target a gene without any taxonomic specificity, for designing oligos from preselected sequences and for checking predesigned oligos. We validated the pipeline on four commercially available microbial mock communities using PhyloPrimer to design genus- and species-specific primers for the detection of Streptococcus species in the mock communities. The software performed well on these mock microbial communities and can be found at https://www.cerealsdb.uk.net/cerealgenomics/phyloprimer. creator: Gilda Varliero creator: Jared Wray creator: Cédric Malandain creator: Gary Barker uri: https://doi.org/10.7717/peerj.11120 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2021 Varliero et al. title: Evidence of integumentary scale diversity in the late Jurassic Sauropod Diplodocus sp. from the Mother’s Day Quarry, Montana link: https://peerj.com/articles/11202 last-modified: 2021-04-29 description: The life appearance of dinosaurs is a hotly debated topic in the world of paleontology, especially when it comes to dinosaur integument. In the case of sauropods, however, the topic is harder to properly discuss due to the limited amount of fossilized skin impressions that have been discovered. Thus far, the fossil record of sauropod integument fossils include titanosaur embryos from Patagonia, possible keratinous diplodocid dorsal spines, track ways with foot impressions, and other isolated skin impressions found in association with sauropod body fossils. Several prominent integument fossils have been found at the Mother’s Day Quarry, located in the Bighorn Basin, Montana. These discoveries may bring new important information about diplodocids, specifically Diplodocus sp. Here we describe newly uncovered fossilized skin that gives evidence of scale diversity in the genus Diplodocus. The scales themselves represent tubercles, and exhibit various shapes including rectangular, ovoid, polygonal, and globular scales. The tubercles are small in size, the biggest of which only reach about 10mm in length. Considering how diverse the scale shapes are in such a small area of skin, it is possible that these distinct scale shapes may represent a transition on the body from one region to another: perhaps from the abdomen to dorsal side, or abdomen to shoulder. Based on analysis of extant integument and scale orientation of crocodilians, it is possible to hypothesize on the location of the integument relative to the body as well as the size and relative maturational status of the individual. creator: Tess Gallagher creator: Jason Poole creator: Jason P. Schein uri: https://doi.org/10.7717/peerj.11202 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2021 Gallagher et al. title: DNA-based diversity assessment reveals a new coral barnacle, Cantellius alveoporae sp. nov. (Balanomorpha: Pyrgomatidae) exclusively associated with the high latitude coral Alveopora japonica in the waters of southern Korea link: https://peerj.com/articles/11284 last-modified: 2021-04-29 description: In the present study, the Indo-Pacific coral associated barnacle Cantellius euspinulosum (Broch, 1931) was found to have cryptic species in Korea, Taiwan and other regions based on molecular studies. However, the original specimens of C. euspinulosum from Broch have not been previously described or illustrated, making it difficult to assign which cryptic species to the original C. euspinulosum. The original specimen of C. euspinulosum was examined and illustrated here, and the species identity of C. cf. euspinulosum collected from Jejudo Island in the present study and other cryptic species (based on literature illustrations) in the Indo-Pacific were evaluated.C. euspinulosum from Singapore, Java, Mergui Archipelago in Andaman Sea and Nha Trang represented the C. euspinulosum identified by Broch (1931). It is a generalist on Acropora, Favia, Favites, Leptoria, Montipora, Pachyseris and Pocillipora corals and distributed in the Indo-Pacific region. Morphological examination and DNA sequencing (COI, 12S DNA sequences) in the present study showed that C. cf. euspinulosum from Jejudo Island, Korea represents a distinct species, herein named C. alveoporae sp. nov. Cantellius alveroporae sp. nov. is a specialist species that only grows on Alveopora and also present in Palau, and Ogasawara Island in Japan. Cantellius cf. euspinuloum in Taiwan, the Moscos Island, and Australia belong to several other distinct species awaiting further morphological and molecular studies. At least five cryptic species of C. euspinulosum were identified in the present study, including both specialist and generalists. creator: Hyun Kyong Kim creator: Benny K.K. Chan creator: Sung Joon Song creator: Jong Seong Khim uri: https://doi.org/10.7717/peerj.11284 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2021 Kim et al. title: Identification of QTL for barley grain size link: https://peerj.com/articles/11287 last-modified: 2021-04-29 description: BackgroundBarley grain size is one of the key factors determining storage capacity during grain filling. Large, well-filled grains also have a high malt extract potential. Grain size is a complex quantitative trait and can be easily affected by environmental factors thus the identification of genes controlling the trait and the use of molecular markers linked to the genes in breeding program is the most effective way of improving grain size.MethodsGrain sizes of 188 doubled-haploid (DH) lines derived from the cross of a Japanese malting barley variety (Naso Nijo) and a Chinese feed barley variety (TX9425) were obtained from three different sites in two consecutive years. The average data were used for identifying QTL for grain size.ResultsA total of four significant QTL were identified for grain length (GL) and three for grain width (GW). The two major GL QTL are located at similar positions to the QTL for malt extract on 2H and uzu gene on 3H, respectively. However, the GL QTL on 2H is more likely a different one from the malt extract QTL as most of the candidate genes are located outside the fine mapped QTL region for malt extract. The GL QTL on 3H is closely linked with uzu gene but not due to a pleiotropic effect of uzu. The three QTL for grain width on 1H, 2H and 5H, respectively, were located at same position to those for GL. creator: Junmei Wang creator: Xiaojian Wu creator: Wenhao Yue creator: Chenchen Zhao creator: Jianming Yang creator: Meixue Zhou uri: https://doi.org/10.7717/peerj.11287 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2021 Wang et al. title: Evaluation of circulating tumor cells as a prognostic biomarker for early recurrence in stage II–III breast cancer patients using CytoSorter® system: a retrospective study link: https://peerj.com/articles/11366 last-modified: 2021-04-29 description: PurposeCirculating tumor cells (CTCs) are known to be associated with late recurrence and poor prognosis in breast cancer (BC). Different CTC enrichment platforms have different CTC cut-off values for poor prognosis. This study aimed to evaluate whether preoperative CTCs could be a prognostic factor for early recurrence of disease in BC patients with resectable tumors, and to ascertain the CTC cut-off value for early recurrence with CytoSorter® CTC system.MethodsThirty-six stage II and III BC patients who had preoperative (pre-op) CTC detection and underwent a mastectomy or lumpectomy for curative intent between January and May 2018 were enrolled in this retrospective study. CTC detection was performed using CytoSorter® CTC system. Correlations of patients’ demographics, clinicopathological characteristics, adjuvant therapies and CTCs with relapse and survival were evaluated.ResultsCTCs were detected in 32 out of 36 patients before surgery. Nine patients developed relapses during follow-up, and seven of them were distant recurrence. Univariate analysis showed that CTCs were correlated with two-year recurrence free survival (RFS) and distant RFS (D-RFS) (P = 0.013 and 0.029, respectively). Two-year RFS and D-RFS were 85.2% and 88.9%, respectively, for patients with <4 CTCs, while 44.4% and 55.6%, respectively, for patients with ≧4 CTCs. In multivariate analysis, only CTC was shown to be correlated with two-year RFS (HR: 0.219, 95% CI: [0.058–0.82], P = 0.024) and D-RFS (HR: 0.218, 95% CI [0.048–0.977], P = 0.047).ConclusionBC patients with pre-op CTCs ≥4 per four mL of blood have significantly reduced two-year RFS and D-RFS. A pre-op CTC cut-off of four per four mL of blood was found for CytoSorter® to identify BC patients with a higher risk for early recurrence. creator: Lidan Jin creator: Wan-Hung Fan creator: Yi Luan creator: Meiqiong Wu creator: Wenhe Zhao uri: https://doi.org/10.7717/peerj.11366 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2021 Jin et al. title: How the fear of COVID-19 changed the way we look at human faces link: https://peerj.com/articles/11380 last-modified: 2021-04-29 description: Do we look at persons currently or previously affected by COVID-19 the same way as we do with healthy ones? In this eye-tracking study, we investigated how participants (N = 54) looked at faces of individuals presented as “COVID-19 Free”, “Sick with COVID-19”, or “Recovered from COVID-19”. Results showed that participants tend to look at the eyes of COVID-19-free faces longer than at those of both COVID-19-related faces. Crucially, we also found an increase of visual attention for the mouth of the COVID-19-related faces, possibly due to the threatening characterisation of such area as a transmission vehicle for SARS-CoV-2. Thus, by detailing how people dynamically changed the way of looking at faces as a function of the perceived risk of contagion, we provide the first evidence in the literature about the impact of the pandemic on the most basic level of social interaction. creator: Giovanni Federico creator: Donatella Ferrante creator: Francesco Marcatto creator: Maria Antonella Brandimonte uri: https://doi.org/10.7717/peerj.11380 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2021 Federico et al. title: The role of orthographic neighbourhood effects in lateralized lexical decision: a replication study and meta-analysis link: https://peerj.com/articles/11266 last-modified: 2021-04-28 description: The effect of orthographic neighbourhood size (N) on lexical decision reaction time differs when words are presented in the left or right visual fields. Evidence suggests a facilitatory N effect (i.e., faster reaction times for words with larger neighbourhoods) in the left visual field. However, the N effect in the right visual field remains controversial: it may have a weaker facilitative role or it may even be inhibitory. In a pre-registered online experiment, we replicated the interaction between N and visual field and provided support for an inhibitory N effect in the right visual field. We subsequently conducted a pre-registered systematic review and meta-analysis to synthesise the available evidence and determine the direction of N effects across visual fields. Based on the evidence, it would seem the effect is inhibitory in the right visual field. Furthermore, the size of the N effect is considerably smaller in the right visual field. Both studies revealed considerable heterogeneity between participants and studies, and we consider the implications of this for future work. creator: Adam J. Parker creator: Ciara Egan creator: Jack H. Grant creator: Sophie Harte creator: Brad T. Hudson creator: Zoe V.J. Woodhead uri: https://doi.org/10.7717/peerj.11266 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2021 Parker et al.