Comparison of human papillomavirus (HPV) detection in urine and cervical swab samples using the HPV GenoArray Diagnostic assay
Human papillomavirus (HPV) is the leading cause of cervical cancer. Urine-based HPV testing offers a simple and non-invasive method because of its increasing acceptance. A total of 164 pairs of cervical swab and urine samples from Thai women who underwent cervical cancer screening were used for HPV testing with HPV GenoArray Diagnostic Kits. The overall concordance percentage for HPV detection in the cervical swab and urine samples was 65.2%. The HPV genotypes most commonly detected were HPV16 and HPV18. An analysis of the urine samples and a second analysis of the cervical swab samples showed that the differences in the overall HPV detection rate between women with normal and abnormal cytology were not significant (p > 0.05). Urine samples processed with the GenoArray assay is an alternative for women who decline to undergo Pap smear even though it is not ideal as the first-line screening option.
Nilyanimit et al. (2017) Comparison of human papillomavirus (HPV) detection in urine and cervical swab samples using the HPV GenoArray Diagnostic assay. PeerJ 5:e3910 https://doi.org/10.7717/peerj.3910
Histamine-2 receptor antagonist famotidine modulates cardiac stem cell characteristics in hypertensive heart disease
Background Cardiac stem cells (CSCs) play a vital role in cardiac homeostasis. A decrease in the efficiency of cardiac stem cells is speculated in various cardiac abnormalities. The maintenance of a healthy stem cell population is essential for the prevention of adverse cardiac remodeling leading to cardiac failure. Famotidine, a histamine-2 receptor antagonist, is currently used to treat ulcers of the stomach and intestines. In repurposing the use of the drug, reduction of cardiac hypertrophy and improvement in cardiac function of spontaneously hypertensive rats (SHR) was reported by our group. Given that stem cells are affected in cardiac pathologies, the effect of histamine-2 receptor antagonism on CSC characteristics was investigated. Methods To examine whether famotidine has a positive effect on CSCs, spontaneously hypertensive rats (SHR) treated with the drug were sacrificed; and CSCs isolated from atrial appendages was evaluated. Six-month-old male SHRs were treated with famotidine (30 mg/kg/day) for two months. The effect of famotidine treatment on migration, proliferation and survival of CSCs was compared with untreated SHRs and normotensive Wistar rats. Results Functional efficiency of CSCs from SHR was compromised relative to that in Wistar rat. Famotidine increased the migration and proliferation potential, along with retention of stemness of CSCs in treated SHRs. Cellular senescence and oxidative stress were also reduced. The expression of H2R was unaffected by the treatment. Discussion As anticipated, CSCs from SHRs were functionally impaired. Stem cell attributes of famotidine-treated SHRs was comparable to that of Wistar rats. Therefore, in addition to being cardioprotective, the histamine 2 receptor antagonist modulated cardiac stem cells characteristics. Restoration of stem cell efficiency by famotidine is possibly mediated by reduction of oxidative stress as the expression of H2R was unaffected by the treatment. Maintenance of healthy stem cell population is suggested as a possible mechanism underlying the cardioprotective effect of famotidine.
Saheera et al. (2017) Histamine-2 receptor antagonist famotidine modulates cardiac stem cell characteristics in hypertensive heart disease. PeerJ 5:e3882 https://doi.org/10.7717/peerj.3882
Influence of exercise duration on cardiorespiratory responses, energy cost and tissue oxygenation within a 6 hour treadmill run
Purpose The physiological mechanisms for alterations in oxygen utilization ( $\dot {\mathrm{V }}{\mathrm{O}}_{2}$ V ̇ O 2 ) and the energy cost of running (Cr) during prolonged running are not completely understood, and could be linked with alterations in muscle and cerebral tissue oxygenation. Methods Eight trained ultramarathon runners (three women; mean ± SD; age 37 ± 7 yr; maximum $\dot {\mathrm{V }}{\mathrm{O}}_{2}$ V ̇ O 2 60 ± 15 mL min−1 kg−1) completed a 6 hr treadmill run (6TR), which consisted of four modules, including periods of moderate (3 min at 10 km h−1, 10-CR) and heavy exercise intensities (6 min at 70% of maximum $\dot {\mathrm{V }}{\mathrm{O}}_{2}$ V ̇ O 2 , HILL), separated by three, 100 min periods of self-paced running (SP). We measured $\dot {\mathrm{V }}{\mathrm{O}}_{2}$ V ̇ O 2 , minute ventilation ( ${\dot {\mathrm{V }}}_{\mathrm{E}}$ V ̇ E ), ventilatory efficiency ( ${\dot {\mathrm{V }}}_{\mathrm{E}}:\dot {\mathrm{V }}{\mathrm{O}}_{2}$ V ̇ E : V ̇ O 2 ), respiratory exchange ratio (RER), Cr, muscle and cerebral tissue saturation index (TSI) during the modules, and heart rate (HR) and perceived exertion (RPE) during the modules and SP. Results Participants ran 58.3 ± 10.5 km during 6TR. Speed decreased and HR and RPE increased during SP. Across the modules, HR and $\dot {\mathrm{V }}{\mathrm{O}}_{2}$ V ̇ O 2 increased (10-CR), and RER decreased (10-CR and HILL). There were no significant changes in ${\dot {\mathrm{V }}}_{\mathrm{E}}$ V ̇ E , ${\dot {\mathrm{V }}}_{\mathrm{E}}:\dot {\mathrm{V }}{\mathrm{O}}_{2}$ V ̇ E : V ̇ O 2 , Cr, TSI and RPE across the modules. Conclusions In the context of positive pacing (decreasing speed), increased cardiac drift and perceived exertion over the 6TR, we observed increased RER and increased HR at moderate and heavy exercise intensity, increased $\dot {\mathrm{V }}{\mathrm{O}}_{2}$ V ̇ O 2 at moderate intensity, and no effect of exercise duration on ventilatory efficiency, energy cost of running and tissue oxygenation.
Kerhervé et al. (2017) Influence of exercise duration on cardiorespiratory responses, energy cost and tissue oxygenation within a 6 hour treadmill run. PeerJ 5:e3694 https://doi.org/10.7717/peerj.3694
Independent evolution of tetraloop in enterovirus oriL replicative element and its putative binding partners in virus protein 3C
Background Enteroviruses are small non-enveloped viruses with a (+) ssRNA genome with one open reading frame. Enterovirus protein 3C (or 3CD for some species) binds the replicative element oriL to initiate replication. The replication of enteroviruses features a low-fidelity process, which allows the virus to adapt to the changing environment on the one hand, and requires additional mechanisms to maintain the genome stability on the other. Structural disturbances in the apical region of oriL domain d can be compensated by amino acid substitutions in positions 154 or 156 of 3C (amino acid numeration corresponds to poliovirus 3C), thus suggesting the co-evolution of these interacting sequences in nature. The aim of this work was to understand co-evolution patterns of two interacting replication machinery elements in enteroviruses, the apical region of oriL domain d and its putative binding partners in the 3C protein. Methods To evaluate the variability of the domain d loop sequence we retrieved all available full enterovirus sequences (>6, 400 nucleotides), which were present in the NCBI database on February 2017 and analysed the variety and abundance of sequences in domain d of the replicative element oriL and in the protein 3C. Results A total of 2,842 full genome sequences was analysed. The majority of domain d apical loops were tetraloops, which belonged to consensus YNHG (Y = U/C, N = any nucleotide, H = A/C/U). The putative RNA-binding tripeptide 154–156 (Enterovirus C 3C protein numeration) was less diverse than the apical domain d loop region and, in contrast to it, was species-specific. Discussion Despite the suggestion that the RNA-binding tripeptide interacts with the apical region of domain d, they evolve independently in nature. Together, our data indicate the plastic evolution of both interplayers of 3C-oriL recognition.
Prostova et al. (2017) Independent evolution of tetraloop in enterovirus oriL replicative element and its putative binding partners in virus protein 3C. PeerJ 5:e3896 https://doi.org/10.7717/peerj.3896
Cryptic biodiversity and phylogeographic patterns of Seychellois Ligia isopods
Ligia isopods are conspicuous inhabitants of rocky intertidal habitats exhibiting several biological traits that severely limit their dispersal potential. Their presence in patchy habitats and low vagility may lead to long term isolation, allopatric isolation and possible cryptic speciation. Indeed, various species of Ligia have been suggested to represent instead cryptic species complexes. Past studies; however, have largely focused in Eastern Pacific and Atlantic species of Ligia, leaving in doubt whether cryptic diversity occurs in other highly biodiverse areas. The Seychelles consists of 115 islands of different ages and geological origins spread across the western Indian Ocean. They are well known for their rich biodiversity with recent reports of cryptic species in terrestrial Seychellois organisms. Despite these studies, it is unclear whether coastal invertebrates from the Seychelles harbor any cryptic diversity. In this study, we examined patterns of genetic diversity and isolation within Ligia isopods across the Seychelles archipelago by characterizing individuals from locations across both inner and outer islands of the Seychelles using mitochondrial and nuclear markers. We report the presence of highly divergent lineages of independent origin. At Aldabra Atoll, we uncovered a lineage closely related to the Ligia vitiensis cryptic species complex. Within the inner islands of Cousine, Silhouette, and Mahé we detected the presence of two moderately divergent and geographically disjunct lineages most closely related to Ligia dentipes. Our findings suggest that the Seychelles may harbor at least three novel species of Ligia in need of description and that these species may have originated independently.
Santamaria et al. (2017) Cryptic biodiversity and phylogeographic patterns of Seychellois Ligia isopods. PeerJ 5:e3894 https://doi.org/10.7717/peerj.3894
Benchmark datasets for phylogenomic pipeline validation, applications for foodborne pathogen surveillance
Background As next generation sequence technology has advanced, there have been parallel advances in genome-scale analysis programs for determining evolutionary relationships as proxies for epidemiological relationship in public health. Most new programs skip traditional steps of ortholog determination and multi-gene alignment, instead identifying variants across a set of genomes, then summarizing results in a matrix of single-nucleotide polymorphisms or alleles for standard phylogenetic analysis. However, public health authorities need to document the performance of these methods with appropriate and comprehensive datasets so they can be validated for specific purposes, e.g., outbreak surveillance. Here we propose a set of benchmark datasets to be used for comparison and validation of phylogenomic pipelines. Methods We identified four well-documented foodborne pathogen events in which the epidemiology was concordant with routine phylogenomic analyses (reference-based SNP and wgMLST approaches). These are ideal benchmark datasets, as the trees, WGS data, and epidemiological data for each are all in agreement. We have placed these sequence data, sample metadata, and “known” phylogenetic trees in publicly-accessible databases and developed a standard descriptive spreadsheet format describing each dataset. To facilitate easy downloading of these benchmarks, we developed an automated script that uses the standard descriptive spreadsheet format. Results Our “outbreak” benchmark datasets represent the four major foodborne bacterial pathogens (Listeria monocytogenes, Salmonella enterica, Escherichia coli, and Campylobacter jejuni) and one simulated dataset where the “known tree” can be accurately called the “true tree”. The downloading script and associated table files are available on GitHub: https://github.com/WGS-standards-and-analysis/datasets. Discussion These five benchmark datasets will help standardize comparison of current and future phylogenomic pipelines, and facilitate important cross-institutional collaborations. Our work is part of a global effort to provide collaborative infrastructure for sequence data and analytic tools—we welcome additional benchmark datasets in our recommended format, and, if relevant, we will add these on our GitHub site. Together, these datasets, dataset format, and the underlying GitHub infrastructure present a recommended path for worldwide standardization of phylogenomic pipelines.
Timme et al. (2017) Benchmark datasets for phylogenomic pipeline validation, applications for foodborne pathogen surveillance. PeerJ 5:e3893 https://doi.org/10.7717/peerj.3893
Hearing assessment during deep brain stimulation of the central nucleus of the inferior colliculus and dentate cerebellar nucleus in rat
Background Recently it has been shown in animal studies that deep brain stimulation (DBS) of auditory structures was able to reduce tinnitus-like behavior. However, the question arises whether hearing might be impaired when interfering in auditory-related network loops with DBS. Methods The auditory brainstem response (ABR) was measured in rats during high frequency stimulation (HFS) and low frequency stimulation (LFS) in the central nucleus of the inferior colliculus (CIC, n = 5) or dentate cerebellar nucleus (DCBN, n = 5). Besides hearing thresholds using ABR, relative measures of latency and amplitude can be extracted from the ABR. In this study ABR thresholds, interpeak latencies (I–III, III–V, I–V) and V/I amplitude ratio were measured during off-stimulation state and during LFS and HFS. Results In both the CIC and the CNBN groups, no significant differences were observed for all outcome measures. Discussion DBS in both the CIC and the CNBN did not have adverse effects on hearing measurements. These findings suggest that DBS does not hamper physiological processing in the auditory circuitry.
Smit et al. (2017) Hearing assessment during deep brain stimulation of the central nucleus of the inferior colliculus and dentate cerebellar nucleus in rat. PeerJ 5:e3892 https://doi.org/10.7717/peerj.3892
Genome methylation and regulatory functions for hypoxic adaptation in Tibetan chicken embryos
Tibetan chickens have unique adaptations to the extreme high-altitude environment that they inhabit. Epigenetic DNA methylation affects many biological processes, including hypoxic adaptation; however, the regulatory genes for DNA methylation in hypoxic adaptation remain unknown. In this study, methylated DNA immunoprecipitation with high-throughput sequencing (MeDIP-seq) was used to provide an atlas of the DNA methylomes of the heart tissue of hypoxic highland Tibetan and lowland Chahua chicken embryos. A total of 31.2 gigabases of sequence data were generated from six MeDIP-seq libraries. We identified 1,049 differentially methylated regions (DMRs) and 695 related differentially methylated genes (DMGs) between the two chicken breeds. The DMGs are involved in vascular smooth muscle contraction, VEGF signaling pathway, calcium signaling pathway, and other hypoxia-related pathways. Five candidate genes that had low methylation (EDNRA, EDNRB2, BMPR1B, BMPRII, and ITGA2) might play key regulatory roles in the adaptation to hypoxia in Tibetan chicken embryos. Our study provides significant explanations for the functions of genes and their epigenetic regulation for hypoxic adaptation in Tibetan chickens.
Zhang et al. (2017) Genome methylation and regulatory functions for hypoxic adaptation in Tibetan chicken embryos. PeerJ 5:e3891 https://doi.org/10.7717/peerj.3891
voomDDA: discovery of diagnostic biomarkers and classification of RNA-seq data
RNA-Seq is a recent and efficient technique that uses the capabilities of next-generation sequencing technology for characterizing and quantifying transcriptomes. One important task using gene-expression data is to identify a small subset of genes that can be used to build diagnostic classifiers particularly for cancer diseases. Microarray based classifiers are not directly applicable to RNA-Seq data due to its discrete nature. Overdispersion is another problem that requires careful modeling of mean and variance relationship of the RNA-Seq data. In this study, we present voomDDA classifiers: variance modeling at the observational level (voom) extensions of the nearest shrunken centroids (NSC) and the diagonal discriminant classifiers. VoomNSC is one of these classifiers and brings voom and NSC approaches together for the purpose of gene-expression based classification. For this purpose, we propose weighted statistics and put these weighted statistics into the NSC algorithm. The VoomNSC is a sparse classifier that models the mean-variance relationship using the voom method and incorporates voom’s precision weights into the NSC classifier via weighted statistics. A comprehensive simulation study was designed and four real datasets are used for performance assessment. The overall results indicate that voomNSC performs as the sparsest classifier. It also provides the most accurate results together with power-transformed Poisson linear discriminant analysis, rlog transformed support vector machines and random forests algorithms. In addition to prediction purposes, the voomNSC classifier can be used to identify the potential diagnostic biomarkers for a condition of interest. Through this work, statistical learning methods proposed for microarrays can be reused for RNA-Seq data. An interactive web application is freely available at http://www.biosoft.hacettepe.edu.tr/voomDDA/.
Zararsiz et al. (2017) voomDDA: discovery of diagnostic biomarkers and classification of RNA-seq data. PeerJ 5:e3890 https://doi.org/10.7717/peerj.3890
The isolation and identification of pathogenic fungi from Tessaratoma papillosa Drury (Hemiptera: Tessaratomidae)
Background Litchi stink-bug, Tessaratoma papillosa Drury (Hemiptera: Tessaratomidae), is one of the most widespread and destructive pest species on Litchi chinensis Sonn and Dimocarpus longan Lour in Southern China. Inappropriate use of chemical pesticides has resulted in serious environmental problems and food pollution. Generating an improved Integrated Pest Management (IPM) strategy for litchi stink-bug in orchard farming requires development of an effective biological control agent. Entomopathogenic fungi are regarded as a vital ecological factor in the suppression of pest populations under field conditions. With few effective fungi and pathogenic strains available to control litchi stink-bug, exploration of natural resources for promising entomopathogenic fungi is warranted. Methods & Results In this study, two pathogenic fungi were isolated from cadavers of adult T. papillosa. They were identified as Paecilomyces lilacinus and Beauveria bassiana by morphological identification and rDNA-ITS homogeneous analysis. Infection of T. papillosa with B. bassiana and P. lilacinus occurred initially from the antennae, metameres, and inter-segmental membranes. Biological tests showed that the two entomopathogenic fungi induced high mortality in 2nd and 5th instar nymphs of T. papillosa. B. bassiana was highly virulent on 2nd instar nymphs of T. papillosa, with values for cadaver rate, LC50 and LT50 of 88.89%, 1.92 × 107 conidia/mL and 4.34 days respectively. Discussion This study provides two valuable entomopathogenic fungi from T. papillosa. This finding suggests that the highly virulent P. lilacinus and B. bassiana play an important role in the biocontrol of T. papillosa in China. These pathogenic fungi had no pollution or residue risk, and could provide an alternative option for IPM of litchi stink-bug.
Meng et al. (2017) The isolation and identification of pathogenic fungi from Tessaratoma papillosa Drury (Hemiptera: Tessaratomidae). PeerJ 5:e3888 https://doi.org/10.7717/peerj.3888