Developmental exposure to the DE-71 mixture of polybrominated diphenyl ether (PBDE) flame retardants induce a complex pattern of endocrine disrupting effects in rats
Polybrominated diphenyl ethers (PBDEs) are legacy compounds with continued widespread human exposure. Despite this, developmental toxicity studies of DE-71, a mixture of PBDEs, are scarce and its potential for endocrine disrupting effects in vivo is not well covered. To address this knowledge gap, we carried out a developmental exposure study with DE-71. Pregnant Wistar rat dams were exposed to 0, 40 or 60 mg/kg bodyweight/day from gestation day 7 to postnatal day 16, and both sexes were examined. Developmental exposure affected a range of reproductive toxicity endpoints. Effects were seen for both male and female anogenital distances (AGD), with exposed offspring of either sex displaying around 10% shorter AGD compared to controls. Both absolute and relative prostate weights were markedly reduced in exposed male offspring, with about 40% relative to controls. DE-71 reduced mammary gland outgrowth, especially in male offspring. These developmental in vivo effects suggest a complex effect pattern involving anti-androgenic, anti-estrogenic and maybe estrogenic mechanisms depending on tissues and developmental stages. Irrespective of the specific underlying mechanisms, these in vivo results corroborate that DE-71 causes endocrine disrupting effects and raises concern for the effects of PBDE-exposure on human reproductive health, including any potential long-term consequences of disrupted mammary gland development.
Environmental Contamination and Remediation
Ramhøj et al. (2022) Developmental exposure to the DE-71 mixture of polybrominated diphenyl ether (PBDE) flame retardants induce a complex pattern of endocrine disrupting effects in rats. PeerJ 10:e12738 https://doi.org/10.7717/peerj.12738
Predicting continuous ground reaction forces from accelerometers during uphill and downhill running: a recurrent neural network solution
Background Ground reaction forces (GRFs) are important for understanding human movement, but their measurement is generally limited to a laboratory environment. Previous studies have used neural networks to predict GRF waveforms during running from wearable device data, but these predictions are limited to the stance phase of level-ground running. A method of predicting the normal (perpendicular to running surface) GRF waveform using wearable devices across a range of running speeds and slopes could allow researchers and clinicians to predict kinetic and kinematic variables outside the laboratory environment. Purpose We sought to develop a recurrent neural network capable of predicting continuous normal (perpendicular to surface) GRFs across a range of running speeds and slopes from accelerometer data. Methods Nineteen subjects ran on a force-measuring treadmill at five slopes (0°, ±5°, ±10°) and three speeds (2.5, 3.33, 4.17 m/s) per slope with sacral- and shoe-mounted accelerometers. We then trained a recurrent neural network to predict normal GRF waveforms frame-by-frame. The predicted versus measured GRF waveforms had an average ± SD RMSE of 0.16 ± 0.04 BW and relative RMSE of 6.4 ± 1.5% across all conditions and subjects. Results The recurrent neural network predicted continuous normal GRF waveforms across a range of running speeds and slopes with greater accuracy than neural networks implemented in previous studies. This approach may facilitate predictions of biomechanical variables outside the laboratory in near real-time and improves the accuracy of quantifying and monitoring external forces experienced by the body when running.
Alcantara et al. (2022) Predicting continuous ground reaction forces from accelerometers during uphill and downhill running: a recurrent neural network solution. PeerJ 10:e12752 https://doi.org/10.7717/peerj.12752
Efficacy of bakuchiol-garlic combination against virulent genes of Candida albicans
Background Polymicrobial biofilms are notorious for causing intraoral tissue destruction. Streptococcus sanguinis and Streptococcus mitis, commensals of oral cavities, have been found co-existing with C. albicans in resistant oral infections. There is an urgent need to find alternative treatment options. This study aims to assess the efficacy of garlic (G) and bakuchiol (Bk) combination against candida virulent genes and their subsequently secreted proteins. Methods In vitro single species biofilms of C. albicans, and mixed species biofilms formed in combination with streptococci were exposed to bakuchiol and garlic extract (Bk+G). Gene expression of agglutinin-like sequence (ALS1), (ALS3), adhesin-like wall proteins (HWP1) and aspartyl proteinases (SAP5) were determined using qPCR and their subsequent proteins were assessed through Western blotting. Results Virulent genes were significantly downregulated in single species biofilms when they were treated with Bk+G combination. However, Bk+G did not have significant effect on ALS1 and HWP1 gene in polymicrobial biofilms. ALS3 and SAP5 were significantly downregulated in Bk+G treated polymicrobial biofilm. Similar results were portrayed in Western blotting. Conclusion Bk+G combination exhibited antimicrobial effects against single and mixed species biofilms. The findings might provide insights for treating resistant candida infections. This combination could potentially serve as an herbal alternative to traditional antifungals following further research.
Fahim et al. (2022) Efficacy of bakuchiol-garlic combination against virulent genes of Candida albicans. PeerJ 10:e12251 https://doi.org/10.7717/peerj.12251
Role of miR-100-5p and CDC25A in breast carcinoma cells
Objective To inquiry about mechanism of miR-100-5p/CDC25A axis in breast carcinoma (BC), thus offering a new direction for BC targeted treatment. Methods qRT-PCR was employed to explore miR-100-5p and CDC25A mRNA levels. Western blot was employed for detecting protein expression of CDC25A. Targeting relationship of miR-100-5p and CDC25A was verified by dual-luciferase assay. In vitro experiments were used for assessment of cell functions. Results In BC tissue and cells, miR-100-5p was significantly lowly expressed (P < 0.05) while CDC25A was highly expressed. Besides, miR-100-5p downregulated CDC25A level. miR-100-5p had a marked influence on the prognosis of patients. The forced miR-100-5p expression hindered BC cell proliferation, migration and invasion, and facilitated cell apoptosis. Upregulated miR-100-5p weakened promotion of CDC25A on BC cell growth. Conclusion Together, these findings unveiled that CDC25A may be a key target of miR-100-5p that mediated progression of BC cells. Hence, miR-100-5p overexpression or CDC25A suppression may contribute to BC diagnosis.
Li et al. (2022) Role of miR-100-5p and CDC25A in breast carcinoma cells. PeerJ 10:e12263 https://doi.org/10.7717/peerj.12263
Characteristics of Central American brocket deer resting sites in a tropical mountain cloud forest in eastern Mexico
The Central American brocket deer is a vulnerable species. Geographically isolated populations have been affected by poaching and habitat fragmentation, leading to local extinctions. It is therefore important to understand this species’ habitat characteristics, particularly of resting sites, which play a crucial role in survival and fitness. We describe the characteristics and distribution patterns of Central American brocket deer resting sites at the microhabitat and landscape scales in San Bartolo Tutotepec, Hidalgo, México. We conducted eight bimonthly field surveys between November 2017 and March 2019, consisting of 32 transects of 500 m length to search for fecal pellets, footprints, scrapes, and browsed plants. At each resting site we identified, we measured canopy closure, horizontal thermal cover, protection from predators for fawns and adults, escape routes, slope from the ground, presence of scrapes, cumulative importance value of the edible plant species, and distance from the resting site to the nearest water resource to characterize the site at the microhabitat scale. At the landscape scale, we identified the type of biotope, elevation, aspect, and slope. We compared all of these parameters from resting sites with a paired randomly selected site to serve as a control. We performed a multiple logistic regression to identify the parameters associated with the resting sites and a point pattern analysis to describe their distribution. We characterized 43 resting sites and their corresponding control plots. At the microhabitat scale, resting sites were associated with higher vertical thermal cover, more concealment cover, more escape routes, more edible plant species, higher slope from the ground, and closer distance to water resources. At the landscape scale, resting sites were associated with beech forest, oak forest, secondary forest, and ravine biotopes and negatively associated with pine forest, houses, and roads. Resting sites had an aggregated spatial pattern from 0 to 900 m, but their distribution was completely random at larger scales. Our study revealed that Central American brocket deer selected places with specific characteristics to rest, at both microhabitat and landscape scales. We therefore suggest that existing habitat be increased by reforesting with native species—particularly Mexican beech forest and oak forest—to improve the deer’s conservation status in the study area.
Muñoz Vazquez et al. (2022) Characteristics of Central American brocket deer resting sites in a tropical mountain cloud forest in eastern Mexico. PeerJ 10:e12587 https://doi.org/10.7717/peerj.12587
Comparative genomics of the black rot pathogen Xanthomonas campestris pv. campestris and non-pathogenic co-inhabitant Xanthomonas melonis from Trinidad reveal unique pathogenicity determinants and secretion system profiles
Black-rot disease caused by the phytopathogen Xanthomonas campestris pv. campestris (Xcc) continues to have considerable impacts on the productivity of cruciferous crops in Trinidad and Tobago and the wider Caribbean region. While the widespread occurrence of resistance of Xcc against bactericidal agrochemicals can contribute to the high disease burdens, the role of virulence and pathogenicity features of local strains on disease prevalence and severity has not been investigated yet. In the present study, a comparative genomic analysis was performed on 6 pathogenic Xcc and 4 co-isolated non-pathogenic Xanthomonas melonis (Xmel) strains from diseased crucifer plants grown in fields with heavy chemical use in Trinidad. Native isolates were grouped into two known and four newly assigned ribosomal sequence types (rST). Mobile genetic elements were identified which belonged to the IS3, IS5 family, Tn3 transposon, resolvases, and tra T4SS gene clusters. Additionally, exogenous plasmid derived sequences with origins from other bacterial species were characterised. Although several instances of genomic rearrangements were observed, native Xcc and Xmel isolates shared a significant level of structural homology with reference genomes, Xcc ATCC 33913 and Xmel CFBP4644, respectively. Complete T1SS hlyDB, T2SS, T4SS vir and T5SS xadA, yapH and estA gene clusters were identified in both species. Only Xmel strains contained a complete T6SS but no T3SS. Both species contained a complex repertoire of extracellular cell wall degrading enzymes. Native Xcc strains contained 37 T3SS and effector genes but a variable and unique profile of 8 avr, 4 xop and 1 hpa genes. Interestingly, Xmel strains contained several T3SS effectors with low similarity to references including avrXccA1 (~89%), hrpG (~73%), hrpX (~90%) and xopAZ (~87%). Furthermore, only Xmel genomes contained a CRISPR-Cas I-F array, but no lipopolysaccharide wxc gene cluster. Xmel strains were confirmed to be non-pathogenic by pathogenicity assays. The results of this study will be useful to guide future research into virulence mechanisms, agrochemical resistance, pathogenomics and the potential role of the co-isolated non-pathogenic Xanthomonas strains on Xcc infections.
Ramnarine et al. (2022) Comparative genomics of the black rot pathogen Xanthomonas campestris pv. campestris and non-pathogenic co-inhabitant Xanthomonas melonis from Trinidad reveal unique pathogenicity determinants and secretion system profiles. PeerJ 10:e12632 https://doi.org/10.7717/peerj.12632
Assessment of health-related quality of life in hypertensive hemodialysis patients
Background and Objectives Globally, the prevalence of hypertension (HTN) with the coexistence of chronic kidney disease (CKD) is increasing, resulting in poor quality of life. The main objective of the study was to measure the health-related quality of life (HRQoL) of hypertensive hemodialysis patients. Methods A multicenter follow-up study was carried out in six public and two private dialysis centers in Pakistan. A total of 517 hypertensive hemodialysis patients responded by completing the questionnaire at baseline and two subsequent phases. The quality of life of these patients was assessed using the EQ-5D-5L questionnaire (a standardized instrument for measuring generic health status). Statistical analysis was done using a multivariate linear regression model, Friedman test and Kruskal Wallis test. Results The majority of patients (58.2%) had normal body mass index and about 60.5% of the patients were taking less salt due to HTN. Friedman test gave the statistically significant results (p ≤ 0.001) in systolic blood pressure (BP), diastolic BP and EQ-5D visual analogue scale (VAS) score between three phases (initial visit, first follow-up and second follow-up). A significant improvement was observed in self-care and usual activities from initial visit to first follow-up (p < 0.05). The most problematic dimension among the hypertensive patients with CKD was pain/discomfort (86.5%). Conclusions HTN with coexisting CKD in hemodialysis patients severely affected HRQoL. Pain/discomfort was the most problematic dimension among the participants.
Aslam et al. (2022) Assessment of health-related quality of life in hypertensive hemodialysis patients. PeerJ 10:e12690 https://doi.org/10.7717/peerj.12690
Land-use history impacts spatial patterns and composition of woody plant species across a 35-hectare temperate forest plot
Land-use history is the template upon which contemporary plant and tree populations establish and interact with one another and exerts a legacy on the structure and dynamics of species assemblages and ecosystems. We use the first census (2010–2014) of a 35-ha forest-dynamics plot at the Harvard Forest in central Massachusetts to describe the composition and structure of the woody plants in this plot, assess their spatial associations within and among the dominant species using univariate and bivariate spatial point-pattern analysis, and examine the interactions between land-use history and ecological processes. The plot includes 108,632 live stems ≥ 1 cm in diameter (2,215 individuals/ha) and 7,595 standing dead stems ≥ 5 cm in diameter. Live tree basal area averaged 42.25 m2/ha, of which 84% was represented by Tsuga canadensis (14.0 m2/ ha), Quercus rubra (northern red oak; 9.6 m2/ ha), Acer rubrum (7.2 m2/ ha) and Pinus strobus (eastern white pine; 4.4 m2/ ha). These same four species also comprised 78% of the live aboveground biomass, which averaged 245.2 Mg/ ha. Across all species and size classes, the forest contains a preponderance (> 80,000) of small stems (<10-cm diameter) that exhibit a reverse-J size distribution. Significant spatial clustering of abundant overstory species was observed at all spatial scales examined. Spatial distributions of A. rubrum and Q. rubra showed negative intraspecific correlations in diameters up to at least a 150-m spatial lag, likely indicative of crowding effects in dense forest patches following intensive past land use. Bivariate marked point-pattern analysis, showed that T. canadensis and Q. rubra diameters were negatively associated with one another, indicating resource competition for light. Distribution and abundance of the common overstory species are predicted best by soil type, tree neighborhood effects, and two aspects of land-use history: when fields were abandoned in the late 19th century and the succeeding forest types recorded in 1908. In contrast, a history of intensive logging prior to 1950 and a damaging hurricane in 1938 appear to have had little effect on the distribution and abundance of present-day tree species. Our findings suggest that current day composition and structure are still being influenced by anthropogenic disturbances that occurred over a century ago.
Orwig et al. (2022) Land-use history impacts spatial patterns and composition of woody plant species across a 35-hectare temperate forest plot. PeerJ 10:e12693 https://doi.org/10.7717/peerj.12693
Identification of the occurrence and potential mechanisms of heterotopic ossification associated with 17-beta-estradiol targeting MKX by bioinformatics analysis and cellular experiments
Background Tendon heterotopic ossification (HO) is a common condition occurring secondary to tendon injury or surgical trauma that significantly affects the patient’s quality of life. The treatment of tendon HO remains challenging due to a lack of clarity regarding the pathological mechanism. Mohawk (MKX) is a key factor in preventing tendon HO; however, its upstream regulatory mechanism remains to be understood. This study aimed to identify potential compounds that target and regulate MKX and explore their functional mechanisms. Methods Bioinformatics analysis of MKX-related compounds and proteins was performed based on data from the STITCH and OncoBinder databases. Subsequently, the SymMap database was used to study MKX-related traditional Chinese medicine drugs and symptoms. Next, the OncoBinder genomic and proteomic discovery model was applied to identify potential regulators of MKX. The analytical tool Expert Protein Analysis System for proteomics was used to predict the three-dimensional structure of MKX, and the AutoDockTools software was used to identify pockets of activity at potential sites for molecular docking. Furthermore, we evaluated the effect of different doses of 17-beta-estradiol on bone marrow-derived mesenchymal stem cells (BM-MSCs). Results By predicting the three-dimensional structure of MKX and simulating molecular docking, Pro-Tyr and 17-beta-Estradiol were found to target and bind to MKX. Analysis of the STITCH and OncoBinder databases showed that MKX had a significant regulatory correlation with suppressor interacting 3 A/histone deacetylase 1 (SIN3A/HDAC1). The GO and KEGG pathway enrichment analysis revealed that the functions of MKX and its associated proteins were mainly enriched in osteogenic-related pathways. Assessment of the proliferation of BM-MSCs revealed that 17-beta-estradiol possibly upregulated the mRNA expression of the HDAC1-SIN3A/BMP pathway-related RUNX2, thereby promoting the proliferation of BM-MSCs. Conclusions The compounds Pro-Tyr and 17-beta-Estradiol may bind to MKX and thus affect the interaction of MKX with SIN3A/HDAC1.
Zhang et al. (2022) Identification of the occurrence and potential mechanisms of heterotopic ossification associated with 17-beta-estradiol targeting MKX by bioinformatics analysis and cellular experiments. PeerJ 10:e12696 https://doi.org/10.7717/peerj.12696
First report of fatty acids in Mimosadiplotricha bee pollen with in vitro lipase inhibitory activity
Bee pollen (BP) is full of nutrients and phytochemicals, and so it is widely used as a health food and alternative medicine. Its composition and bioactivity mainly depend on the floral pollens. In this work, BP collected by Apis mellifera with different monoculture flowering crops (BP1-6) were used. The types of floral pollen in each BP were initially identified by morphology, and subsequently confirmed using molecular phylogenetic analysis. Data from both approaches were consistent and revealed each BP to be monofloral and derived from the flowers of Camellia sinensis L., Helianthus annuus L., Mimosa diplotricha, Nelumbo nucifera, Xyris complanata, and Ageratum conyzoides for BP1 to BP6, respectively. The crude extracts of all six BPs were prepared by sequential partition with methanol, dichloromethane (DCM), and hexane. The crude extracts were then tested for the in vitro (i) α-amylase inhibitory, (ii) acetylcholinesterase inhibitory (AChEI), and (iii) porcine pancreatic lipase inhibitory (PPLI) activities in terms of the percentage enzyme inhibition and half maximum inhibitory concentration (IC50). The DCM partitioned extract of X. complanata BP (DCMXBP) had the highest active α-amylase inhibitory activity with an IC50 value of 1,792.48 ± 50.56 µg/mL. The DCM partitioned extracts of C. sinensis L. BP (DCMCBP) and M. diplotricha BP (DCMMBP) had the highest PPLI activities with an IC50 value of 458.5 ± 13.4 and 500.8 ± 24.8 µg/mL, respectively), while no crude extract showed any marked AChEI activity. Here, the in vitro PPLI activity was focused on. Unlike C. sinensis L. BP, there has been no previous report of M. diplotricha BP having PPLI activity. Hence, DCMMBP was further fractionated by silica gel 60 column chromatography, pooling fractions with the same thin layer chromatography profile. The pooled fraction of DCMMBP2-1 was found to be the most active (IC50 of 52.6 ± 3.5 µg/mL), while nuclear magnetic resonance analysis revealed the presence of unsaturated free fatty acids. Gas chromatography with flame-ionization detection analysis revealed the major fatty acids included one saturated acid (palmitic acid) and two polyunsaturated acids (linoleic and linolenic acids). In contrast, the pooled fraction of DCMMBP2-2 was inactive but pure, and was identified as naringenin, which has previously been reported to be present in M. pigra L. Thus, it can be concluded that naringenin was compound marker for Mimosa BP. The fatty acids in BP are nutritional and pose potent PPLI activity.
Khongkarat et al. (2022) First report of fatty acids in Mimosadiplotricha bee pollen with in vitro lipase inhibitory activity. PeerJ 10:e12722 https://doi.org/10.7717/peerj.12722