Lymph node detection in MR Lymphography: false positive reduction using multi-view convolutional neural networks
Purpose To investigate whether multi-view convolutional neural networks can improve a fully automated lymph node detection system for pelvic MR Lymphography (MRL) images of patients with prostate cancer. Methods A fully automated computer-aided detection (CAD) system had been previously developed to detect lymph nodes in MRL studies. The CAD system was extended with three types of 2D multi-view convolutional neural networks (CNN) aiming to reduce false positives (FP). A 2D multi-view CNN is an efficient approximation of a 3D CNN, and three types were evaluated: a 1-view, 3-view, and 9-view 2D CNN. The three deep learning CNN architectures were trained and configured on retrospective data of 240 prostate cancer patients that received MRL images as the standard of care between January 2008 and April 2010. The MRL used ferumoxtran-10 as a contrast agent and comprised at least two imaging sequences: a 3D T1-weighted and a 3D T2*-weighted sequence. A total of 5089 lymph nodes were annotated by two expert readers, reading in consensus. A first experiment compared the performance with and without CNNs and a second experiment compared the individual contribution of the 1-view, 3-view, or 9-view architecture to the performance. The performances were visually compared using free-receiver operating characteristic (FROC) analysis and statistically compared using partial area under the FROC curve analysis. Training and analysis were performed using bootstrapped FROC and 5-fold cross-validation. Results Adding multi-view CNNs significantly (p < 0.01) reduced false positive detections. The 3-view and 9-view CNN outperformed (p < 0.01) the 1-view CNN, reducing FP from 20.6 to 7.8/image at 80% sensitivity. Conclusion Multi-view convolutional neural networks significantly reduce false positives in a lymph node detection system for MRL images, and three orthogonal views are sufficient. At the achieved level of performance, CAD for MRL may help speed up finding lymph nodes and assessing them for potential metastatic involvement.
Debats et al. (2019) Lymph node detection in MR Lymphography: false positive reduction using multi-view convolutional neural networks. PeerJ 7:e8052 https://doi.org/10.7717/peerj.8052
Long-term study of behaviors of two cohabiting sea urchin species, Mesocentrotus nudus and Strongylocentrotus intermedius, under conditions of high food quantity and predation risk in situ
Background In the predator–sea urchin–macrophyte trophic cascade, the ecological effect of sea urchins as grazers depends both on their density and the changes in foraging activity, which are influenced by various disturbing factors. However, the complete duration of the alarm reactions of echinoids has not been studied until now. Here, we tested a hypothesis that two cohabiting sea urchins, Mesocentrotus nudus and Strongylocentrotus intermedius, which differ morphologically, might display different behavioral responses to high hydrodynamic activity and predation. Methods We used continuous time-lapse video recording to clarify behavioral patterns of M. nudus and S. intermedius in presence of a large quantity of food (the kelp Saccharina japonica) but under different weather conditions and different types of predation threat: (1) calm weather conditions, (2) stormy weather conditions, (3) predation risk associated with the presence of several sea star species and (4) predation risk associated with an alarm stimulus (crushed conspecifics or heterospecifics). Three separate video recording experiments (134 days in total) were conducted under field conditions. Video recording analysis was performed to determine the number of specimens of each sea urchin species in the cameras’ field of view, size of sea urchins’ groups, movement patterns and the duration of the alarm responses of both sea urchin species. Results We showed that in the presence of kelp, M. nudus and S. intermedius exhibited both similar and different behavioral responses to hydrodynamics and predation threat. Under calm weather, movement patterns of both echinoids were similar but M. nudus exhibited the higher locomotion speed and distance traveled. Furthermore, S. intermedius but not M. nudus tended to group near the food substrate. The stormy weather caused a sharp decrease in movement activity followed by escape response in both echinoids. Six starfish species failed to predate on healthy sea urchins of either species and only a few attacks on ailing S. intermedius specimens were successful. The alarm response of S. intermedius lasted approximately 90 h and 20 h for starfish attacks on ailing conspecifics and for simulated attacks (crushed conspecifics or heterospecifics), respectively and involved several phases: (1) flight response, (2) grouping close to the food, (3) leaving the food and (4) return to the food. Phase three was the more pronounced in a case of starfish attack. M. nudus only responded to crushed conspecifics and exhibited no grouping behavior but displayed fast escape (during 4 h) and prolonged (up to 19 days) avoidance of the food source. This outcome is the longest alarm response reported for sea urchins. Discussion The most interesting finding is that two cohabiting sea urchin species, M. nudus and S. intermedius, display different alarm responses to predation threat. Both alarm responses are interpreted as defensive adaptations against visual predators.
Zhadan et al. (2019) Long-term study of behaviors of two cohabiting sea urchin species, Mesocentrotus nudus and Strongylocentrotus intermedius, under conditions of high food quantity and predation risk in situ. PeerJ 7:e8087 https://doi.org/10.7717/peerj.8087
Munidopsis species (Crustacea: Decapoda: Munidopsidae) from carcass falls in Weijia Guyot, West Pacific, with recognition of a new species based on integrative taxonomy
Several squat lobster specimens of the genus Munidopsis were collected from an artificially placed carcass fall (cow bones) on Weijia Guyot in the western Pacific Ocean. Based on morphological comparisons and molecular analysis, three specimens were confirmed as juveniles of M. albatrossae Pequegnat & Pequegnat, 1973, which represents the first record of this species in the western Pacific. The other specimens collected are newly described as Munidopsis spinifrons sp. nov., which is distinguished from the closely related species in having a spinose rostrum and basal lateral eyespine on the eyestalk. The M. albatrossae from Weijia Guyot exhibited very low genetic distances when compared with a conspecific sample from Monterey Bay, USA, and the closely related species M. aries (A. Milne Edwards, 1880) from the northeastern Atlantic. A phylogenetic tree based on the mtCOI gene shows M. spinifrons sp. nov. as sister to M. vrijenhoeki Jones & Macpherson, 2007 and M. nitida (A. Milne Edwards, 1880), although M. vrijenhoeki presents a complex relationship with other species in the clade. The systematic status of the new species and the closely related species are discussed.
Dong et al. (2019) Munidopsis species (Crustacea: Decapoda: Munidopsidae) from carcass falls in Weijia Guyot, West Pacific, with recognition of a new species based on integrative taxonomy. PeerJ 7:e8089 https://doi.org/10.7717/peerj.8089
Comprehensive analysis of differentially expressed microRNAs and mRNAs in MDBK cells expressing bovine papillomavirus E5 oncogene
Delta bovine papillomaviruses (δBPVs) causes fibropapillomas or bladder cancer in cattle. E5 is the major oncogene of δBPVs; however, the influence that E5 oncogene has on host microRNA (miRNA) and mRNA expression profiles remains little elucidated. In the present study, small RNA sequencing and RNA sequencing were used to explore alterations in miRNAs and mRNAs in E5 over-expressing Madin-Darby bovine kidney (MDBK) cells compared with controls. In total, 77 miRNAs (including 30 bovine-derived miRNAs) and 223 genes were differentially expressed (DE) following E5 overexpression. The dysregulated genes were mainly involved in metabolic and biosynthetic processes. We constructed a potential miRNA-gene regulatory network from the differentially expressed genes (DEGs) and DE miRNAs. Finally, 22 DEGs and nine DE miRNAs were selected for RT-qPCR validation. Of these, downregulation of six miRNAs, bta-miR-34c, bta-miR-122, bta-miR-195, bta-miR-449b, bta-miR-2425-5p, and bta-miR-2428-3p were confirmed; In addition, upregulation of 16 genes, ACSS2, DDIT4, INHBE, INSIG1, PNRC1, PSAT1, PSPH, PYCR1, SC4MOL, SLC34A2, SCD, SPARC, IDI1, PCK2, HMGCS1, and SMIM14 and downregulation of two genes, BATF3 and WFDC2 were confirmed. Specially, bta-miR-34c and bta-miR-449b potentially regulated PYCR1 and DDIT4, which were involved in cancer progression and angiogenesis. Our study presented for the first time the comprehensive miRNA and mRNA alterations in MDBK cells expressing the BPV E5 oncogene, providing new insights into the tumorigenesis induced by BPV E5.
Pang et al. (2019) Comprehensive analysis of differentially expressed microRNAs and mRNAs in MDBK cells expressing bovine papillomavirus E5 oncogene. PeerJ 7:e8098 https://doi.org/10.7717/peerj.8098
Comparative morphology and trophic ecology in a population of the polymorphic lizard Sceloporus minor (Squamata: Phrynosomatidae) from central Mexico
Polymorphism among individuals of the same population has generally been linked to alternative reproductive tactics, where different morphs can exhibit differences in their morphological, ecological, and behavioral attributes. These differences may result in a divergence in diet between morphs due to differential exploitation of habitat, morphological differences that influence prey selection, or differential energy expenditure that results in different nutritional needs. The present study analyzes the morphology (morphometry and body mass) and diet of red and yellow male morphs in a population (El Enzuelado) of the lizard Sceloporus minor from central Mexico. No differences between morphs were found for any of the morphometric variables analyzed (snout-vent length, tail length, jaw length, jaw width, head length, head width, head height, tibia length, femur length, forearm length and ventral patch length). In both morphs, allometric growth was observed in all body features analyzed, as well as in morphometric features of the head across seasons. Analysis of stomach contents showed that the diet of red males was composed of 12 categories of prey, while that of yellow males was composed of 10 categories; those categories of diet not shared between morphs (e.g., Isoptera, Psocoptera) were consumed by their respective morph in very low proportions. Categories of diet with the highest values of food importance for both groups were Coleoptera, Orthoptera, and leaves; a similar pattern was seen across seasons. This, in turn, is reflected in low niche breadth values for each morph and a very high niche overlap. There were no significant differences between morphs overall, or between morphs per season, in the weight and volume of stomach contents or in the number of prey items found in stomachs; however, differences in these variables across all males (independent of morph) were recorded between seasons. Likewise, no significant correlations were found between body size (snout-vent length) and the volume of stomach contents for either morph or between lizard mandibular dimensions and the volume of stomach contents for red morph males. For the yellow morph, prey volume unexpectedly decreased significantly with jaw size rather than increasing as expected. Overall, this study adds new information about the morphology and feeding of males in this species, and suggests that in this population, color morphs lack the morphological and ecological differences found in some other species of polymorphic lizard.
García-Rosales et al. (2019) Comparative morphology and trophic ecology in a population of the polymorphic lizard Sceloporus minor (Squamata: Phrynosomatidae) from central Mexico. PeerJ 7:e8099 https://doi.org/10.7717/peerj.8099
The first North American Propterodon (Hyaenodonta: Hyaenodontidae), a new species from the late Uintan of Utah
The carnivorous mammalian fauna from the Uintan (late middle Eocene) of North America remains relatively poorly documented. This is unfortunate, as this is a critical interval in the transition from “creodont” to carnivoran dominated carnivore guilds. This study reports a new species from the Uinta Formation of the Uinta Basin, Utah, the first North American species of the otherwise Asian hyaenodont genus Propterodon. The new species, Propterodon witteri, represented by a dentary with M2-3 from the late Uintan Leota Quarry, is larger than the well-known P. morrisi and P. tongi and has a larger M3 talonid, but is otherwise very similar. A phylogenetic analysis of hyaenodont interrelationships recovers P. witteri as a hyaenodontine but is generally poorly resolved. A relationship between Hyaenodontinae and Oxyaenoides, recovered by many recent analyses, is not supported. Among the Asian species of Propterodon, P. pishigouensis is reidentified as a machaeroidine oxyaenid and recombined as Apataelurus pishigouensis new combination. Isphanatherium ferganensis may also represent an Asian machaeroidine. Identification of a North American species of Propterodon and an Asian Apataelurus increases the similarity of North American Uintan and Asian Irdinmanhan faunas and suggests that there was substantial exchange of carnivorous fauna during the late middle Eocene.
Zack (2019) The first North American Propterodon (Hyaenodonta: Hyaenodontidae), a new species from the late Uintan of Utah. PeerJ 7:e8136 https://doi.org/10.7717/peerj.8136
Accumulation of di-2-ethylhexyl phthalate from polyvinyl chloride flooring into settled house dust and the effect on the bacterial community
Di-2-ethylhexyl phthalate (DEHP) is a plasticizer used in consumer products and building materials, including polyvinyl chloride flooring material. DEHP adsorbs from material and leaches into soil, water, or dust and presents an exposure risk to building occupants by inhalation, ingestion, or absorption. A number of bacterial isolates are demonstrated to degrade DEHP in culture, but bacteria may be susceptible to it as well, thus this study examined the relation of DEHP to bacterial communities in dust. Polyvinyl chloride flooring was seeded with homogenized house dust and incubated for up to 14 days, and bacterial communities in dust were identified at days 1, 7, and 14 using the V3–V4 regions of the bacterial 16S rRNA gene. DEHP concentration in dust increased over time, as expected, and bacterial richness and Shannon diversity were negatively correlated with DEHP concentration. Some sequence variants of Bacillus, Corynebacterium jeddahense, Streptococcus, and Peptoniphilus were relatively more abundant at low concentrations of DEHP, while some Sphingomonas, Chryseobacterium, and a member of the Enterobacteriaceae family were relatively more abundant at higher concentrations. The built environment is known to host lower microbial diversity and biomass than natural environments, and DEHP or other chemicals indoors may contribute to this paucity.
Environmental Contamination and Remediation
Velazquez et al. (2019) Accumulation of di-2-ethylhexyl phthalate from polyvinyl chloride flooring into settled house dust and the effect on the bacterial community. PeerJ 7:e8147 https://doi.org/10.7717/peerj.8147
TLR4 polymorphisms may increase susceptibility to periodontitis in Pg-positive individuals
Objective To investigate the correlation between the single nucleotide polymorphisms (SNPs) in the toll-like receptor 4 (TLR4) gene and the susceptibility to chronic periodontitis. Design 241 Chinese subjects from the cohort of Beijing Shijingshan Community were recruited. Buccal swab samples, the whole unstimulated saliva and periodontal clinical parameters were collected. Human DNA extracted from buccal swab samples were used for genotyping eight SNPs of the TLR4 gene (rs11536889, rs1927906, rs1927911, rs2149356, rs4986790, rs4986791, rs2737190, rs787384) by the Sequenom MassARRAY system. Porphyromonas gingivalis (P. gingivalis) was detected from the deposition of the whole unstimulated saliva through polymerase chain reaction (PCR) method based on 16S rRNA. The correlation between SNPs of TLR4 and chronic periodontitis susceptibility in the whole subjects and the patients detected with P. gingivalis was investigated. Results The variants of rs4986790 and rs4986791 were not found in 241 Chinese subjects. Moreover, there was no significant difference in the distribution of theother6 SNPs of TLR4 between groups of none/mild -periodontitis and moderate/severe-periodontitis subjects. When combined with P. gingivalis infection, rs1927911 (TT/CC+CT), rs2149356 (TT/GG+GT) and rs2737190 (GG/AA+AG) were independent risk factors of chronic periodontitis. Conclusion Three SNPs of TLR4, i.e., rs1927911 (TT/CC+CT), rs2149356 (TT/GG+GT) and rs2737190 (GG/AA+AG), were associated with moderate/severe chronic periodontitis in Chinese population infected with P. gingivalis. P. gingivalis, which interacted with TLR4 gene plays an important role in the pathogenesis of periodontitis.
Li et al. (2019) TLR4 polymorphisms may increase susceptibility to periodontitis in Pg-positive individuals. PeerJ 7:e7828 https://doi.org/10.7717/peerj.7828
Charcot-Marie-Tooth type 4B2 demyelinating neuropathy in miniature Schnauzer dogs caused by a novel splicing SBF2 (MTMR13) genetic variant: a new spontaneous clinical model
Background Charcot-Marie-Tooth (CMT) disease is the most common neuromuscular disorder in humans affecting 40 out of 100,000 individuals. In 2008, we described the clinical, electrophysiological and pathological findings of a demyelinating motor and sensory neuropathy in Miniature Schnauzer dogs, with a suspected autosomal recessive mode of inheritance based on pedigree analysis. The discovery of additional cases has followed this work and led to a genome-wide association mapping approach to search for the underlying genetic cause of the disease. Methods For genome wide association screening, genomic DNA samples from affected and unaffected dogs were genotyped using the Illumina CanineHD SNP genotyping array. SBF2 and its variant were sequenced using primers and PCRs. RNA was extracted from muscle of an unaffected and an affected dog and RT-PCR performed. Immunohistochemistry for myelin basic protein was performed on peripheral nerve section specimens. Results The genome-wide association study gave an indicative signal on canine chromosome 21. Although the signal was not of genome-wide significance due to the small number of cases, the SBF2 (also known as MTMR13) gene within the region of shared case homozygosity was a strong positional candidate, as 22 genetic variants in the gene have been associated with demyelinating forms of Charcot-Marie-Tooth disease in humans. Sequencing of SBF2 in cases revealed a splice donor site genetic variant, resulting in cryptic splicing and predicted early termination of the protein based on RNA sequencing results. Conclusions This study reports the first genetic variant in Miniature Schnauzer dogs responsible for the occurrence of a demyelinating peripheral neuropathy with abnormally folded myelin. This discovery establishes a genotype/phenotype correlation in affected Miniature Schnauzers that can be used for the diagnosis of these dogs. It further supports the dog as a natural model of a human disease; in this instance, Charcot-Marie-Tooth disease. It opens avenues to search the biological mechanisms responsible for the disease and to test new therapies in a non-rodent large animal model. In particular, recent gene editing methods that led to the restoration of dystrophin expression in a canine model of muscular dystrophy could be applied to other canine models such as this before translation to humans.
Granger et al. (2019) Charcot-Marie-Tooth type 4B2 demyelinating neuropathy in miniature Schnauzer dogs caused by a novel splicing SBF2 (MTMR13) genetic variant: a new spontaneous clinical model. PeerJ 7:e7983 https://doi.org/10.7717/peerj.7983
Stability of the vaginal, oral, and gut microbiota across pregnancy among African American women: the effect of socioeconomic status and antibiotic exposure
Objective A growing body of research has investigated the human microbiota and pregnancy outcomes, especially preterm birth. Most studies of the prenatal microbiota have focused on the vagina, with fewer investigating other body sites during pregnancy. Although pregnancy involves profound hormonal, immunological and metabolic changes, few studies have investigated either shifts in microbiota composition across pregnancy at different body sites or variation in composition at any site that may be explained by maternal characteristics. The purpose of this study was to investigate: (1) the stability of the vaginal, oral, and gut microbiota from early (8–14 weeks) through later (24–30 weeks) pregnancy among African American women according to measures of socioeconomic status, accounting for prenatal antibiotic use; (2) whether measures of socioeconomic status are associated with changes in microbiota composition over pregnancy; and (3) whether exposure to prenatal antibiotics mediate any observed associations between measures of socioeconomic status and stability of the vaginal, oral, and gut microbiota across pregnancy. Methods We used paired vaginal, oral, or gut samples available for 16S rRNA gene sequencing from two time points in pregnancy (8–14 and 24–30 weeks) to compare within-woman changes in measures of alpha diversity (Shannon and Chao1) and beta-diversity (Bray–Curtis dissimilarity) among pregnant African American women (n = 110). Multivariable linear regression was used to examine the effect of level of education and prenatal health insurance as explanatory variables for changes in diversity, considering antibiotic exposure as a mediator, adjusting for age, obstetrical history, and weeks between sampling. Results For the oral and gut microbiota, there were no significant associations between measures of socioeconomic status or prenatal antibiotic use and change in Shannon or Chao1 diversity. For the vaginal microbiota, low level of education (high school or less) was associated with an increase in Shannon and Chao1 diversity over pregnancy, with minimal attenuation when controlling for prenatal antibiotic use. Conversely, for within-woman Bray–Curtis dissimilarity for early compared to later pregnancy, low level of education and prenatal antibiotics were associated with greater dissimilarity for the oral and gut sites, with minimal attenuation when controlling for prenatal antibiotics, and no difference in dissimilarity for the vaginal site. Conclusions Measures of maternal socioeconomic status are variably associated with changes in diversity across pregnancy for the vaginal, oral, and gut microbiota, with minimal attenuation by prenatal antibiotic exposure. Studies that evaluate stability of the microbiota across pregnancy in association with health outcomes themselves associated with socioeconomic status (such as preterm birth) should incorporate measures of socioeconomic status to avoid finding spurious relationships.
Dunlop et al. (2019) Stability of the vaginal, oral, and gut microbiota across pregnancy among African American women: the effect of socioeconomic status and antibiotic exposure. PeerJ 7:e8004 https://doi.org/10.7717/peerj.8004