title: PeerJ description: Articles published in PeerJ link: https://peerj.com/articles/index.rss3?journal=peerj&page=657 creator: info@peerj.com PeerJ errorsTo: info@peerj.com PeerJ language: en title: Phenotypic spectrum of FGF10-related disorders: a systematic review link: https://peerj.com/articles/14003 last-modified: 2022-09-14 description: FGF10, as an FGFR2b-specific ligand, plays a crucial role during cell proliferation, multi-organ development, and tissue injury repair. The developmental importance of FGF10 has been emphasized by the identification of FGF10 abnormalities in human congenital disorders affecting different organs and systems. Single-nucleotide variants in FGF10 or FGF10-involving copy-number variant deletions have been reported in families with lacrimo-auriculo-dento-digital syndrome, aplasia of the lacrimal and salivary glands, or lethal lung developmental disorders. Abnormalities involving FGF10 have also been implicated in cleft lip and palate, myopia, or congenital heart disease. However, the exact developmental role of FGF10 and large phenotypic heterogeneity associated with FGF10 disruption remain incompletely understood. Here, we review human and animal studies and summarize the data on FGF10 mechanism of action, expression, multi-organ function, as well as its variants and their usefulness for clinicians and researchers. creator: Katarzyna Bzdega creator: Justyna A. Karolak uri: https://doi.org/10.7717/peerj.14003 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2022 Bzdega and Karolak title: 5-Methylindole kills various bacterial pathogens and potentiates aminoglycoside against methicillin-resistant Staphylococcus aureus link: https://peerj.com/articles/14010 last-modified: 2022-09-14 description: Antibiotic resistance of bacterial pathogens has become a severe threat to human health. To counteract antibiotic resistance, it is of significance to discover new antibiotics and also improve the efficacy of existing antibiotics. Here we show that 5-methylindole, a derivative of the interspecies signaling molecule indole, is able to directly kill various Gram-positive pathogens (e.g., Staphylococcus aureus and Enterococcus faecalis) and also Gram-negative ones (e.g., Escherichia coli and Pseudomonas aeruginosa), with 2-methylindole being less potent. Particularly, 5-methylindole can kill methicillin-resistant S. aureus, multidrug-resistant Klebsiella pneumoniae, Mycobacterium tuberculosis, and antibiotic-tolerant S. aureus persisters. Furthermore, 5-methylindole significantly potentiates aminoglycoside antibiotics, but not fluoroquinolones, killing of S. aureus. In addition, 5-iodoindole also potentiates aminoglycosides. Our findings open a new avenue to develop indole derivatives like 5-methylindole as antibacterial agents or adjuvants of aminoglycoside. creator: Zhongyan Li creator: Fengqi Sun creator: Xinmiao Fu creator: Yajuan Chen uri: https://doi.org/10.7717/peerj.14010 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2022 Li et al. title: The emergence of spiraling tracheary element bundles in incompatible grafts link: https://peerj.com/articles/14020 last-modified: 2022-09-14 description: In distantly-related plant grafting, incompatibility often occurs between scion and rootstock, resulting in growth stagnation, and eventually graft failure. In this study, we found that an emergent structure, or the spiraling tracheary element (TE) bundles consisting of TE masses occurring at the graft interface, was extensively present in the highly incompatible interfamilial graft of Brassica napus/Portulaca oleracea (Bn/Po) and Nicotiana benthamiana/Portulaca oleracea (Nb/Po). This special structure mostly appeared in the local area near the grafting union, and the frequency and quantity of the spiraling tracheary element bundles were much higher in the scion than in the rootstock. Nevertheless, only a small portion of Arabidopsis thaliana/Portulaca oleracea (At/Po) interfamilial grafts showed a less spiraled TEs at the grafting union (usually a circular TE), which is consistent with its growth performance. This study consolidated that spiraling TE bundles were an important indicator for graft incompatibility. The possible reason for the formation of spiraling TE bundles in interfamilial grafts was discussed. creator: Huiyan Wu creator: Zhuying Deng creator: Xue Wang creator: Dacheng Liang uri: https://doi.org/10.7717/peerj.14020 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2022 Wu et al. title: The below-ground carbon and nitrogen cycling patterns of different mycorrhizal forests on the eastern Qinghai-Tibetan Plateau link: https://peerj.com/articles/14028 last-modified: 2022-09-14 description: Mycorrhizal fungi can form symbiotic associations with tree species, which not only play an important role in plant survival and growth, but also in soil carbon (C) and nitrogen (N) cycling. However, the understanding of differences in soil C and N cycling patterns among forests with different mycorrhizal types is still incomplete. In order to determine the similarities and differences of soil C and N cycling patterns in different mycorrhizal forest types, three primary forests dominated by ectomycorrhizal (EcM), arbuscular mycorrhizal (AM) and ericoid mycorrhizal (ErM) trees respectively were studied on the eastern Qinghai-Tibetan Plateau. Indicators associated with soil C and N cycling, including leaf litter quality, soil C and N contents, soil C and N fluxes, and soil microbial biomass C and N contents were measured in each mycorrhizal type forest. The results showed that leaf litter quality was significantly lower with high C:N ratio and lignin: N ratio in ErM forest than that in AM and EcM forests. Soil CO2 flux (508.25 ± 65.51 mg m−2 h−1) in AM forest was significantly higher than that in EcM forest (387.18 ± 56.19 mg m−2 h−1) and ErM forest (177.87 ± 58.40 mg m−2 h−1). Furthermore, soil inorganic N content was higher in the AM forest than that in EcM and ErM forests. Soil net N mineralization rate (−0.02 ± 0.03 mg kg−1 d−1) was lower in ErM forest than that in EcM and AM forests. We speculated that AM and EcM forests were relatively characterized by rapid soil C cycling comparing to ErM forest. The soil N cycling in EcM and ErM forests were lower, implying they were ‘organic’ N nutrition patterns, and the pattern in ErM forest was more obvious. creator: Miaomiao Zhang creator: Shun Liu creator: Miao Chen creator: Jian Chen creator: Xiangwen Cao creator: Gexi Xu creator: Hongshuang Xing creator: Feifan Li creator: Zuomin Shi uri: https://doi.org/10.7717/peerj.14028 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2022 Zhang et al. title: A novel virtual reality application for autonomous assessment of cervical range of motion: development and reliability study link: https://peerj.com/articles/14031 last-modified: 2022-09-14 description: BackgroundNeck pain, one of the most common musculoskeletal diseases, affects 222 million people worldwide. The cervical range of motion (CROM) is a tool used to assess the neck’s state across three movement axes: flexo-extension, rotation, and lateral flexion. People with neck pain often have a reduced CROM, and they feel pain at the end-range and/or accompany neck movements with compensatory trunk movements. Virtual reality (VR) setups can track the movement of the head and other body parts in order to create the sensation of immersion in the virtual environment. Using this tracking position information, a CROM assessment can be performed using a VR setup that may be carried out autonomously from the user’s home. The objectives of this study were to develop a VR experience that could be used to perform a CROM assessment, and to evaluate the intra-rater and inter-rater reliability of the CROM measures guided by this VR experience. To the best of our knowledge, a study of this type has not been carried out before.Materials & MethodsA total of 30 asymptomatic adults were assessed using a VR device (HTC Vive Pro Eye™). Two raters provided support with the VR setup, and the participants were guided by the VR experience as they performed the movements. Each rater tested each subject twice, in random order. In addition to a head-mounted display (HMD), a tracker located on the subject’s back was used to measure trunk compensatory movements. The CROM was estimated using only the HMD position and this measurement was corrected using the tracker data. The mean and standard deviation were calculated to characterize the CROM. To evaluate the reliability, the interclass correlation coefficients (ICC) were calculated for intra-rater and inter-rater analysis. The standard error of measurement and minimum detectable change were also calculated. The usability of the VR system was measured using the Spanish version of the System Usability Scale.ResultsThe mean CROM values in each axis of movement were compatible with those described in the literature. ICC values ranged between 0.86 and 0.96 in the intra-rater analysis and between 0.83 and 0.97 in the inter-rater analysis; these values were between good and excellent. When applying the correction of the trunk movements, both the intra-rater and inter-rater ICC values slightly worsened except in the case of the lateral flexion movement, where they slightly improved. The usability score of the CROM assessment/VR system was 86 points, which is an excellent usability score.ConclusionThe reliability of the measurements and the usability of the system indicate that a VR setup can be used to assess CROM. The reliability of the VR setup can be affected by slippage of the HMD or tracker. Both slippage errors are additive, i.e., only when the sum of these two errors is less than the compensatory movement do the measurements improve when considering the tracker data. creator: Jose Angel Santos-Paz creator: Álvaro Sánchez-Picot creator: Ana Rojo creator: Aitor Martín-Pintado-Zugasti creator: Abraham Otero creator: Rodrigo Garcia-Carmona uri: https://doi.org/10.7717/peerj.14031 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2022 Santos-Paz et al. title: The effects of rumen-protected tryptophan (RPT) on production performance and relevant hormones of dairy cows link: https://peerj.com/articles/13831 last-modified: 2022-09-13 description: Tryptophan is an essential amino acid that cannot be synthesized in mammals. Therefore, the dietary supply of tryptophan is critical for the health and production performance (e.g., milk) of mammals. In the present study, 36 lactating Holstein cows were used, of which 24 cows were in the rumen-protected tryptophan (RPT) feeding groups with different doses at 14 g/d and 28 g/d, respectively and 12 cows were in the control group. This approach could avoid dietary tryptophan being degraded by the rumen microorganisms and improve its bioavailability for cows. The results showed that RPT increased milk protein percentage, milk protein yield, milk solid non-fat (SNF), and milk yield. In response to RPT treatment, the levels of melatonin (MT), prolactin (PRL), and insulin-like growth factor-1 (IGF-1) were significantly increased in the serum of cows compared to the controls. RPT feeding improved nutrient utilization efficiency and lactation performance of dairy cows, which enhanced the quality of milk. creator: Hui Ma creator: Songyang Yao creator: Libing Bai creator: Sarvvl Bai creator: Guoshi Liu uri: https://doi.org/10.7717/peerj.13831 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2022 Ma et al. title: High temperature mortality of Wolbachia impacts the sex ratio of the parasitoid Ooencyrtus mirus (Hymenoptera: Encyrtidae) link: https://peerj.com/articles/13912 last-modified: 2022-09-13 description: BackgroundWolbachia bacteria are estimated to occur in more than half of all insect species. In Hymenoptera, Wolbachia often manipulates its host’s reproduction to its own advantage. Wolbachia is likely the reason that males are rare in the uniparental Ooencyrtus mirus Triapitsyn & Power (Hymenoptera: Encyrtidae). The likelihood of producing male offspring can be increased by giving mothers a continuous supply of Bagrada hilaris (Burmeister) (Heteroptera: Pentatomidae) host eggs to parasitize for 2–3 weeks, by feeding the parents antibiotics, or by rearing parent wasps at high temperatures; all variables that have been shown to correlate with depleting Wolbachia titers in other organisms. The purpose of the current study was to determine whether thelytoky in O. mirus is due to Wolbachia, and if so, at what time in development the sex change occurs. We also wished to determine if Wolbachia removal results in the production of intersexes, as in some other hymenopterans. Finally, mating behavior was observed to see if and where it breaks down as a result of the species becoming thelytokous.MethodsFemales were collected from parental lines of O. mirus reared at 26, 30, 31, 32, 33, 34, and 36 °C. The offspring of these females were reared at 26 °C, and their sex-ratio was determined. In a subsequent experiment, the parental generation was switched between 26 °C and 36 °C during development to narrow down the critical period at which changes occurred that subsequently affected the sex-ratio of their offspring.ResultsThe sex ratio was male biased in the offspring of O. mirus parents reared at 34 °C and 36 °C (high temperatures), even if the offspring themselves were reared at 26 °C. The constant temperature at which the percentage of males started to increase after two generations was 31 °C (10% males), rising to 39% males at 33 °C, and 100% males at 34 °C and 36 °C. Lasting more than 2 days, the critical period for the change toward a male biased sex ratio was during the second half of the parent’s development. Molecular diagnostic assays confirmed that O. mirus females contain Wolbachia and males do not. Examination of preserved males and male-female pairs under a dissecting microscope showed no signs of intersex characters. Observation of the mating behavior of live O. mirus showed that males initiate courtship by drumming their antennae on a female’s antennae, but after a few seconds, the females typically turn and walk away. However, a few instances of possible copulation were noted.ConclusionsAs hypothesized, the results indicated that thelytoky in O. mirus is likely mediated by Wolbachia bacteria. To maximize the population growth rate without generating males, the best temperature for mass rearing this species is 30 °C. creator: Nancy R. Power creator: Paul F. Rugman-Jones creator: Richard Stouthamer creator: Fatemeh Ganjisaffar creator: Thomas M. Perring uri: https://doi.org/10.7717/peerj.13912 license: https://creativecommons.org/licenses/by/4.0/ rights: ©2022 Power et al. title: PTC2 region genotypes counteract Biomphalaria glabrata population differences between M-line and BS90 in resistance to infection by Schistosoma mansoni link: https://peerj.com/articles/13971 last-modified: 2022-09-13 description: BackgroundBiomphalaria glabrata is a snail intermediate host for Schistosoma mansoni, a trematode responsible for human schistosomiasis. BS90 is one of the most well studied strains of B. glabrata owing to its high resistance to infection by most strains of S. mansoni. An F2 mapping study from 1999 identified two RAPD markers that associated with what appeared to be single-locus, dominant resistance by the BS90 population relative to the susceptible M-line population. One marker cannot be mapped, but the other, OPM-04, maps to within 5 Mb of PTC2, a region we recently showed has a very large effect on resistance within another snail population challenged by the same strain of parasite (PR1). Here we tested the hypothesis that the PTC2 region contains the causal gene/s that explain the iconic resistance of BS90 snails.MethodsWe used marker-assisted backcrossing to drive the BS90 version of the PTC2 region (+/−~1 Mb on either side) into an M-line (susceptible strain) genetic background, and the M-line version into a BS90 genetic background. We challenged the offspring with PR1-strain schistosomes and tested for effects of allelic variation in the PTC2 region in a common genetic background.ResultsRelative to M-line haplotypes, the BS90 haplotype actually confers enhanced susceptibility. So we reject our original hypothesis. One possible explanation for our result was that the causal gene linked to OPM-04 is near, but not in the PTC2 block that we introgressed into each line. So we used an F2 cross to independently test the effects of the PTC2 and OPM-04 regions in a randomized genetic background. We confirmed that the BS90 haplotype confers increased susceptibility, and we see a similar, although non-significant effect at OPM-04. We discuss possible reasons why our results differed so dramatically from those of the 1999 study. We also present Pacbio assemblies of the PTC2 and flanking region in BS90 and M-line, compare with previously published PTC2 haplotypes, and discuss candidate genes that might be behind the enhanced susceptibility of the BS90 haplotype. creator: Michael S. Blouin creator: Stephanie R. Bollmann creator: Jacob A. Tennessen uri: https://doi.org/10.7717/peerj.13971 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2022 Blouin et al. title: Screening of potential key ferroptosis-related genes in sepsis link: https://peerj.com/articles/13983 last-modified: 2022-09-13 description: BackgroundSepsis leads to multiple organ dysfunction caused by a dysregulated host response to infection with a high incidence and mortality. The effect of ferroptosis on the development of sepsis remains unclear. In this study, we aimed to identify the key ferroptosis-related genes involved in sepsis and further explore the potential biological functions of these ferroptosis-related genes in sepsis using bioinformatics analysis.MethodsThe GSE13904 (from children) and GSE28750 (from adults) datasets were downloaded from the Gene Expression Omnibus (GEO). The ferroptosis-related genes were obtained from the FerrDb database. The ferroptosis-related differentially expressed genes (DEGs) were screened by the limma R package. The DAVID online database or clusterProfiler R package was used for the functional enrichment analysis. Then, the STRING database was used to predict the interactions of proteins, and the CytoHubba plugin of Cytoscape was used to confirm key clustering modules. Then, the miRNAs and lncRNAs associated with the key clustering modules were predicted by miRWalk 2.0 and LncBase v.2 respectively. Finally, we generated a cecal ligation and puncture (CLP) polymicrobial sepsis model in C57 male mice and examined the expression of the mRNAs and noncoding RNAs of interest in peripheral blood leukocytes by PCR during the acute inflammation phase.ResultsIn total, 34 ferroptosis-related DEGs were identified in both adult and pediatric septic patients. These ferroptosis-related DEGs were mainly enriched in inflammatory pathways. Then, a significant clustering module containing eight genes was identified. Among them, the following five genes were closely associated with the MAPK signaling pathway: MAPK14, MAPK8, DUSP1, MAP3K5 and MAPK1. Then, crucial miRNAs and lncRNAs associated with biomarker MAPK-related genes were also identified. In particular, let-7b-5p and NEAT1 were selected as noncoding RNAs of interest because of their correlation with ferroptosis in previous studies. Finally, we examined the mRNAs, miRNAs and lncRNAs of interest using CLP-induced sepsis in peripheral blood leukocytes of mice. The results showed that MAPK14, MAPK8, MAP3K5, MAPK1 and NEAT1 were upregulated, while DUSP1 and let-7b-5p were downregulated in the CLP group compared with the sham group.ConclusionsThe MAPK signaling pathway may play a key role in regulating ferroptosis during sepsis. This study provides a valuable resource for future studies investigating the mechanism of MAPK-related ferroptosis in sepsis. creator: Shunan Cui creator: Kun Niu creator: Yining Xie creator: Shuo Li creator: Wenzhi Zhu creator: Ling Yu creator: Hongyu Tan uri: https://doi.org/10.7717/peerj.13983 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2022 Cui et al. title: Moonlighting proteins in medically relevant fungi link: https://peerj.com/articles/14001 last-modified: 2022-09-13 description: Moonlighting proteins represent an intriguing area of cell biology, due to their ability to perform two or more unrelated functions in one or many cellular compartments. These proteins have been described in all kingdoms of life and are usually constitutively expressed and conserved proteins with housekeeping functions. Although widely studied in pathogenic bacteria, the information about these proteins in pathogenic fungi is scarce, but there are some reports of their functions in the etiological agents of the main human mycoses, such as Candida spp., Paracoccidioides brasiliensis, Histoplasma capsulatum, Aspergillus fumigatus, Cryptococcus neoformans, and Sporothrix schenckii. In these fungi, most of the described moonlighting proteins are metabolic enzymes, such as enolase and glyceraldehyde-3-phosphate dehydrogenase; chaperones, transcription factors, and redox response proteins, such as peroxiredoxin and catalase, which moonlight at the cell surface and perform virulence-related processes, contributing to immune evasion, adhesions, invasion, and dissemination to host cells and tissues. All moonlighting proteins and their functions described in this review highlight the limited information about this biological aspect in pathogenic fungi, representing this a relevant opportunity area that will contribute to expanding our current knowledge of these organisms’ pathogenesis. creator: Verania J. Arvizu-Rubio creator: Laura C. García-Carnero creator: Héctor Manuel Mora-Montes uri: https://doi.org/10.7717/peerj.14001 license: https://creativecommons.org/licenses/by/4.0/ rights: © 2022 Arvizu-Rubio et al.