Testis development in the Japanese eel is affected by photic signals through melatonin secretion
Objective According to reported spawning characteristics of Japanese eel, Anguilla japonica, which exhibit spawning and migration patterns that are synchronized with lunar cycles and photoperiod, we hypothesized that a close association exists between specific photic signals (daylight, daylength, and moonlight) and endocrinological regulation. Given the photic control in melatonin secretion, this hypothesis was tested by investigating whether melatonin signals act as mediators relaying photic signals during testis development in the eel. Methods We examined changes in melatonin-secretion patterns using time-resolved fluorescence immunoassays in sexually immature and mature male Japanese eels under the condition of a new moon (NM) and a full moon (FM). Results The eye and plasma melatonin levels exhibited a nocturnal pattern under a 12-h light: dark cycle (12L12D) or under constant darkness (DD), but not with constant light (LL). Eye melatonin levels were similar under the 12L12D and short-day (9L15D) conditions. In the long-day condition (15L9D), secreted plasma melatonin levels were stable, whereas short-day melatonin secretion began when darkness commenced. Sexual maturation began at 8 weeks following intraperitoneal injection of human chorionic gonadotropin (hCG), and NM exposure led to significantly higher eye and plasma melatonin levels compared with those detected under FM exposure.
Hyeon et al. (2021) Testis development in the Japanese eel is affected by photic signals through melatonin secretion. PeerJ 9:e12289 https://doi.org/10.7717/peerj.12289
The beneficial effect of physical activity on cognitive function in community-dwelling older persons with locomotive syndrome
Background Cognitive decline is closely related to motor decline. Locomotive syndrome (LS) is defined as a state associated with a high risk of requiring support because of locomotive organ disorders, and can be evaluated using a questionnaire. This study aimed to clarify the effectiveness of daily goal-targeted exercise on cognitive function in two different populations classified by scores on the Locomo 25 questionnaire. Methods Seventy community-dwelling older people who participated in a 13-week health class were divided into two populations based on Locomo 25 scores: <7 (non-LS) and ≥7 (LS). Participants were presented with a daily target steps and worked towards that goal. Cognitive function was evaluated using the Japanese version of Addenbrooke’s Cognitive Examination-Revised (ACE-R). Average daily physical activity (exercise [Ex]) for 13 weeks was measured using a portable activity meter. Depression status was assessed using the Geriatric Depression Scale (GDS-15). Results No significant differences were observed in age, years of education, body mass index, smooth muscle mass index, GDS-15 scores, or ACE-R scores between the non-LS and LS populations. Multiple logistic regression analysis showed that Ex (odds ratio = 5.01, p = 0.002) for 13 weeks was significantly associated with increased cognitive function in the LS population. The Ex threshold for the increase in cognitive function based on receiver operating curve analysis was 2.29 metabolic equivalents of task (METs) × h (METs · h/day) (p = 0.047) in the LS population. After 13 weeks, ACE-R scores were significantly higher in the Ex ≥ 2.29 than in the Ex < 2.29 METs · h/day group (p = 0.024, ηp2 = 0.241) in the LS population based on two-way analysis of covariance. Furthermore, a significant increase in the ACE-R memory domain was seen in the Ex ≥ 2.29 group (p = 0.035, ηp2 = 0.213). Conclusions These results suggest that Ex ≥ 2.29 METs · h/day is important for improving cognitive function in LS populations.
Nakamura et al. (2021) The beneficial effect of physical activity on cognitive function in community-dwelling older persons with locomotive syndrome. PeerJ 9:e12292 https://doi.org/10.7717/peerj.12292
The role of zinc transporter proteins as predictive and prognostic biomarkers of hepatocellular cancer
Identification of the key processes involved in the tumor progression, malignancy and the molecular factors which are responsible for the transition of the cirrhotic cells to the tumor cells, contribute to the detection of biomarkers for diagnosis of hepatocellular carcinoma (HCC) at an early stage. According to clinical data, HCC is mostly characterized by a significant decrease in zinc levels. It is strongly implied that zinc deficiency is the major event required in the early stages of tumor formation and development of malignancy. Due to this reason, the definition of the molecular players which have a role in zinc homeostasis and cellular zinc level could give us a clue about the transition state of the cirrhosis to hepatic tumor formation. Despite the well-known implications of zinc in the development of HCCthe correlation of the expression of zinc transporter proteins with tumor progression and malignancy remain largely unknown. In the present study, we evaluated in detail the relationship of zinc deficiency on the prognosis of early HCC patients. In this study, we aimed to test the potential zinc transporters which contribute tothe transformation of cirrhosis to HCCand the progression of HCC. Among the 24 zinc transporter proteins, the proteins to be examined were chosen by using Gene Expression Profiling Interactive Analysis (GEPIA) webpage and RNA-seq analysis using TCGA database. ZIP14 and ZIP5 transporters were found as common differentially expressed genes from both bioinformatic analyses. ZnT1, ZnT7 and ZIP7 transporters have been associated with tumor progression. Relative abundance of ZnT1, ZIP5 and ZIP14 protein level was determined by immunohistochemistry (IHC) in surgically resected liver specimens from 16 HCC patients at different stages. IHC staining intensity was analyzed by using ImageJ software and scored with the histological scoring (H-score) method. The staining of ZnT1 was significantly higher in Grade III comparing to Grade II and Grade I. On the contrary, ZIP14 staining decreased almost 10-foldcomparing to Grade Iand Grade II. ZIP5 staining was detected almost 2-fold higher in cirrhosis than HCC. But ZnT1 staining was observed almost 3-fold lower in cirrhosis comparing to HCC. Intracellular free zinc level was measured by flow cytometry in Hep40 and Snu398 cells using FluoZin-3 dye. The intracellular free zinc level was almost 9-fold decreased in poor differentiated Snu398 HCC cells comparing to well differentiated Hep40 HCC cells.This report establishes for the first time the correlation between the expression pattern of ZIP14, ZnT1 and ZIP5 and significant zinc deficiency which occurs concurrently with the advancing of malignancy. Our results provide new molecular insight into ZnT1, ZIP14 and ZIP5 mediated regulation of cellular zinc homeostasis and indicate that zinc transporters might be important factors and events in HCC malignancy, which can lead to the development of early biomarkers.
Bitirim (2021) The role of zinc transporter proteins as predictive and prognostic biomarkers of hepatocellular cancer. PeerJ 9:e12314 https://doi.org/10.7717/peerj.12314
HLA alleles measured from COVID-19 patient transcriptomes reveal associations with disease prognosis in a New York cohort
Background The Human Leukocyte Antigen (HLA) gene locus plays a fundamental role in human immunity, and it is established that certain HLA alleles are disease determinants. Previously, we have identified prevalent HLA class I and class II alleles, including DPA1*02:02, in two small patient cohorts at the COVID-19 pandemic onset. Methods We have since analyzed a larger public patient cohort data (n = 126 patients) with controls, associated demographic and clinical data. By combining the predictive power of multiple in silico HLA predictors, we report on HLA-I and HLA-II alleles, along with their associated risk significance. Results We observe HLA-II DPA1*02:02 at a higher frequency in the COVID-19 positive cohort (29%) when compared to the COVID-negative control group (Fisher’s exact test [FET] p = 0.0174). Having this allele, however, does not appear to put this cohort’s patients at an increased risk of hospitalization. Inspection of COVID-19 disease severity outcomes, including admission to intensive care, reveal nominally significant risk associations with A*11:01 (FET p = 0.0078) and C*04:01 (FET p = 0.0087). The association with severe disease outcome is especially evident for patients with C*04:01, where disease prognosis measured by mechanical ventilation-free days was statistically significant after multiple hypothesis correction (Bonferroni p = 0.0323). While prevalence of some of these alleles falls below statistical significance after Bonferroni correction, COVID-19 patients with HLA-I C*04:01 tend to fare worse overall. This HLA allele may hold potential clinical value.
Warren et al. (2021) HLA alleles measured from COVID-19 patient transcriptomes reveal associations with disease prognosis in a New York cohort. PeerJ 9:e12368 https://doi.org/10.7717/peerj.12368
Seasonal trends of the polyp expansion and nutritional condition of Alcyonium acaule (Octocorallia, Alcyonacea)
The ecological physiology of anthozoans, as well as their resistance to stressors, are strongly influenced by environmental factors and the availability of resources. The energy budget of anthozoans can vary seasonally in order to find an equilibrium between the available resources and respiration, polyp activity, growth, and reproduction processes. The variation in the biochemical composition of the animal tissues in these organisms results from a combination of the productivity processes of the water column coupled with the reproductive effort and potential starvation periods of the anthozoans. Here, the seasonal variation in the polyp activity of a slow-growing passive suspension feeder, the octocoral Alcyonium acaule, as well as their carbohydrate, protein and lipid contents, was investigated in a warm temperate environment using in-situ observations and biochemical analyses. Polyp activity exhibited a significant variability that was moderately dependent on season, while an aestivation phenomenon in A. acaule (i.e., a resting period in which the anthozoan is not capable of any polyp activity) during the warmer months is clearly observed. Carbohydrate concentrations in the coral species showed a significant increase in the late winter and spring seasons, and the lipid content increased during the spring. A higher abundance of lipids and carbohydrates coincided with a higher primary productivity in the water column, as well as with the octocoral reproduction period. In late autumn, there was a depletion of these biomolecules, with protein levels exhibiting great variability across sampling times. Complex alterations driven by climate change could affect the energy fluxes that depend on the dead or alive particles that are intercepted by marine animal forests. The obtained findings show a food shortage in late summer and autumn of the benthic suspension feeder A. acaule through the integrative descriptors of the ecophysiology of these anthozoans. This research contributes to the knowledge of energy storage capabilities in benthic suspension feeders in general, highlighting the importance of understanding the limits of resistance to starvation periods through these indicators.
Rizzo et al. (2021) Seasonal trends of the polyp expansion and nutritional condition of Alcyonium acaule (Octocorallia, Alcyonacea). PeerJ 9:e12032 https://doi.org/10.7717/peerj.12032
Changes in diversity and composition of rhizosphere bacterial community during natural restoration stages in antimony mine
Background Open pit antimony (Sb) mining causes serious soil pollution, and phytoremediation is a low-cost approach to remediate heavy metal contaminated soil. Rhizosphere bacteria play an important role in ecological restoration in mining areas. There is a knowledge gap on how to find suitable rhizosphere microorganisms to improve the phytoremediation effect. Understanding the differences of rhizosphere bacterial diversity in different restoration stages is helpful to find suitable bacteria for ecological restoration. Methods A method of the substitution of “space” for “time” was used to study the effect of natural restoration on rhizosphere bacterial community. According to the dominant vegetation types (herb, shrub, and tree) in the natural restoration area of Sb mining, the early restoration (ER), middle restoration (MR), and later restoration (LR) from the largest Sb mine (Xikuangshan mine) in the world were selected to evaluate the differences in the composition and diversity of rhizosphere bacteria during three natural restoration stages. Each restoration stage had five samples. To determine the relationship between restoration stages and bacterial diversity in the rhizosphere, high throughput sequencing of PCR amplified were used. Results Alpha diversity, as assessed by Chao indices, appeared lowest in ER but this trend was not seen with other diversity metrics, including the Simpson and Shannon. Beta diversity analysis suggested there were differences in rhizobacterial community structure associate with restoration stage. At the phylum level, natural restoration led to a significant increase in the relative abundance of Actinobacteria in the MR, and a significant decrease in the relative abundance of Patescibacteria in the LR. Additionally, Calditrichaeota, Deferribacteres and Epsilonbacteraeota were only found in ER. At the genus level, the relative abundance of RB41 and Haliangium were highest in LR plots, while that of Bacillus and Gaiella were highest in ER plots. Additionally, the Azorhizobium genus was only detected in the ER phase. Overall, our findings suggested that several rhizosphere microbial communities had significant differences among three natural restoration stages (ER, MR, and LR) and the rhizosphere bacterial communities mainly appeared in the early restoration stage can be preferred for remediation of pollution soil in Xikuangshan.
Environmental Contamination and Remediation
Duan et al. (2021) Changes in diversity and composition of rhizosphere bacterial community during natural restoration stages in antimony mine. PeerJ 9:e12302 https://doi.org/10.7717/peerj.12302
A novel pyroptosis-associated gene signature for immune status and prognosis of cutaneous melanoma
Background Cutaneous melanoma (CM) is a life-threatening destructive malignancy. Pyroptosis significantly correlates with programmed tumor cell death and its microenvironment through active host-tumor crosstalk. However, the prognostic value of pyroptosis-associated gene signatures in CM remains unclear. Methods Gene profiles and clinical data of patients with CM were downloaded from The Cancer Genome Atlas (TCGA) to identify differentially expressed genes associated with pyroptosis and overall survival (OS). We constructed a prognostic gene signature using LASSO analysis, then applied immune cell infiltration scores and Kaplan-Meier, Cox, and pathway enrichment analyses to determine the roles of the gene signature in CM. A validation cohort was collected from the Gene Expression Omnibus (GEO) database. Results Four pyroptosis-associated genes were identified and incorporated into a prognostic gene signature. Integrated bioinformatics findings showed that the signature correlated with patient survival and was associated with tumor growth and metastasis. The results of Gene Set Enrichment Analysis of a risk signature indicated that several enriched pathways are associated with cancer and immunity. The risk signature for immune status significantly correlated with tumor stem cells, the immune microenvironment, immune cell infiltration and immune subtypes. The expression of four pyroptosis genes significantly correlated with the OS of patients with CM and was related to the sensitivity of cancer cells to several antitumor drugs. A signature comprising four genes associated with pyroptosis offers a novel approach to the prognosis and survival of patients with CM and will facilitate the development of individualized therapy.
Wu et al. (2021) A novel pyroptosis-associated gene signature for immune status and prognosis of cutaneous melanoma. PeerJ 9:e12304 https://doi.org/10.7717/peerj.12304
Betulinic acid decreases lipid accumulation in adipogenesis-induced human mesenchymal stem cells with upregulation of PGC-1α and UCP-1 and post-transcriptional downregulation of adiponectin and leptin secretion
Background Controlling cellular functions, including stem cell growth and differentiation, can be the key for the treatment of metabolic disorders, such as type II diabetes mellitus (T2DM). Previously identified as peroxisome proliferator-activated receptor gamma (PPARγ) antagonist, betulinic acid (BA) may have the capability to control stem cell homeostasis, benefiting T2DM treatment. In this study, the effects of BA on osteogenesis and adipogenesis mechanisms of human mesenchymal stem cells (hMSCs) were investigated. Results We observed that BA increased hMSC osteogenesis by enhancing the alkaline phosphatase activity, calcium deposition, and mRNA expressions of osteogenic markers, namely, runt-related transcription factor 2, osteocalcin, and osteopontin. In addition, BA decreased hMSC adipogenesis with the decrease in glycerol-3-phosphate dehydrogenase activity, reduced intracellular lipid accumulations, down-regulated CCAAT-enhancer-binding protein alpha, and suppressed post-transcriptional adiponectin and leptin secretion. BA increased the brown adipocyte characteristics with the increase in the ratio of small lipid droplets and glucose uptake. Furthermore, the mRNA expressions of brown adipocyte markers, namely, PPARγ coactivator one alpha, uncoupling protein 1, and interleukin-6 increased. Conclusions Our results uncovered the mechanisms of how BA improved glucose and lipid metabolisms by decreasing white adipogenesis and increasing brown adipogenesis. Altogether, BA may be used for balancing glucose metabolisms without the potential side effects on bone loss or weight gain.
Senamontree et al. (2021) Betulinic acid decreases lipid accumulation in adipogenesis-induced human mesenchymal stem cells with upregulation of PGC-1α and UCP-1 and post-transcriptional downregulation of adiponectin and leptin secretion. PeerJ 9:e12321 https://doi.org/10.7717/peerj.12321
Characteristics and factors influencing the natural regeneration of Larix principis-rupprechtii seedlings in northern China
Larix principis-rupprechtii is an important and widely distributed species in the mountains of northern China. However, it has inefficient natural regeneration in many stands and difficulty recruiting seedlings and saplings. In this study, we selected six plots with improved naturally-regenerated L. principis-rupprechtii seedlings. A point pattern analysis (pair-correlation function) was applied to identify the spatial distribution pattern and correlation between adult trees and regenerated seedlings mapped through X/Y coordinates. Several possible influencing factors of L. principis-rupprechtii seedlings’ natural regeneration were also investigated. The results showed that the spatial distribution patterns of Larix principis-rupprechtii seedlings were concentrated 0–5 m around adult trees when considering the main univariate distribution type of regeneration. There was a positive correlation at a scale of 1.5–4 m between seedlings and adult trees according to bivariate analyses. When the scale was increased, these relationships were no longer significant. Generally, adult trees raised regenerated L. principis-rupprechtii seedlings at a scale of 1.5–4 m. Principal component analysis showed that the understory herb diversity and litter layer had a negative correlation with the number of regenerated seedlings. There was also a weak relationship between regenerated numbers and canopy density. This study demonstrated that the main factors promoting natural regeneration were litter thickness, herb diversity, and the distance between adult trees and regenerated seedlings. Additionally, these findings will provide a basis for the late-stage and practical management of natural regeneration in northern China’s mountain ranges.
Zhao et al. (2021) Characteristics and factors influencing the natural regeneration of Larix principis-rupprechtii seedlings in northern China. PeerJ 9:e12327 https://doi.org/10.7717/peerj.12327
A docked mutation phenocopies dumpy oblique alleles via altered vesicle trafficking
The Drosophila extracellular matrix protein Dumpy (Dpy) is one of the largest proteins encoded by any animal. One class of dpy mutations produces a characteristic shortening of the wing blade known as oblique (dpyo), due to altered tension in the developing wing. We describe here the characterization of docked (doc), a gene originally named because of an allele producing a truncated wing. We show that doc corresponds to the gene model CG5484, which encodes a homolog of the yeast protein Yif1 and plays a key role in ER to Golgi vesicle transport. Genetic analysis is consistent with a similar role for Doc in vesicle trafficking: docked alleles interact not only with genes encoding the COPII core proteins sec23 and sec13, but also with the SNARE proteins synaptobrevin and syntaxin. Further, we demonstrate that the strong similarity between the doc1 and dpyo wing phenotypes reflects a functional connection between the two genes; we found that various dpy alleles are sensitive to changes in dosage of genes encoding other vesicle transport components such as sec13 and sar1. Doc’s effects on trafficking are not limited to Dpy; for example, reduced doc dosage disturbed Notch pathway signaling during wing blade and vein development. These results suggest a model in which the oblique wing phenotype in doc1 results from reduced transport of wild-type Dumpy protein; by extension, an additional implication is that the dpyo alleles can themselves be explained as hypomorphs.
Kandasamy et al. (2021) A docked mutation phenocopies dumpy oblique alleles via altered vesicle trafficking. PeerJ 9:e12175 https://doi.org/10.7717/peerj.12175