Extending SEQenv: a taxa-centric approach to environmental annotations of 16S rDNA sequences
Understanding how the environment selects a given taxon and the diversity patterns that emerge as a result of environmental filtering can dramatically improve our ability to analyse any environment in depth as well as advancing our knowledge on how the response of different taxa can impact each other and ecosystem functions. Most of the work investigating microbial biogeography has been site-specific, and logical environmental factors, rather than geographical location, may be more influential on microbial diversity. SEQenv, a novel pipeline aiming to provide environmental annotations of sequences emerged to provide a consistent description of the environmental niches using the ENVO ontology. While the pipeline provides a list of environmental terms on the basis of sample datasets and, therefore, the annotations obtained are at the dataset level, it lacks a taxa centric approach to environmental annotation. The work here describes an extension developed to enhance the SEQenv pipeline, which provided the means to directly generate environmental annotations for taxa under different contexts. 16S rDNA amplicon datasets belonging to distinct biomes were selected to illustrate the applicability of the extended SEQenv pipeline. A literature survey of the results demonstrates the immense importance of sequence level environmental annotations by illustrating the distribution of both taxa across environments as well as the various environmental sources of a specific taxon. Significantly enhancing the SEQenv pipeline in the process, this information would be valuable to any biologist seeking to understand the various taxa present in the habitat and the environment they originated from, enabling a more thorough analysis of which lineages are abundant in certain habitats and the recovery of patterns in taxon distribution across different habitats and environmental gradients.
Ijaz et al. (2017) Extending SEQenv: a taxa-centric approach to environmental annotations of 16S rDNA sequences. PeerJ 5:e3827 https://doi.org/10.7717/peerj.3827
Virulence test using nematodes to prescreen Nocardia species capable of inducing neurodegeneration and behavioral disorders
Background Parkinson’s disease (PD) is a disorder characterized by dopaminergic neuron programmed cell death. The etiology of PD remains uncertain—some cases are due to selected genes associated with familial heredity, others are due to environmental exposure to toxic components, but over 90% of cases have a sporadic origin. Nocardia are Actinobacteria that can cause human diseases like nocardiosis. This illness can lead to lung infection or central nervous system (CNS) invasion in both immunocompromised and immunocompetent individuals. The main species involved in CNS are N. farcinica, N. nova, N. brasiliensis and N. cyriacigeorgica. Some studies have highlighted the ability of N. cyriacigeorgica to induce Parkinson’s disease-like symptoms in animals. Actinobacteria are known to produce a large variety of secondary metabolites, some of which can be neurotoxic. We hypothesized that neurotoxic secondary metabolite production and the onset of PD-like symptoms in animals could be linked. Methods Here we used a method to screen bacteria that could induce dopaminergic neurodegeneration before performing mouse experiments. Results The nematode Caenorhabditis elegans allowed us to demonstrate that Nocardia strains belonging to N. cyriacigeorgica and N. farcinica species can induce dopaminergic neurodegeneration. Strains of interest involved with the nematodes in neurodegenerative disorders were then injected in mice. Infected mice had behavioral disorders that may be related to neuronal damage, thus confirming the ability of Nocardia strains to induce neurodegeneration. These behavioral disorders were induced by N. cyriacigeorgica species (N. cyriacigeorgica GUH-2 and N. cyriacigeorgica 44484) and N. farcinica 10152. Discussion We conclude that C. elegans is a good model for detecting Nocardia strains involved in neurodegeneration. This model allowed us to detect bacteria with high neurodegenerative effects and which should be studied in mice to characterize the induced behavioral disorders and bacterial dissemination.
Bernardin Souibgui et al. (2017) Virulence test using nematodes to prescreen Nocardia species capable of inducing neurodegeneration and behavioral disorders. PeerJ 5:e3823 https://doi.org/10.7717/peerj.3823
Clinical outcomes of residual or recurrent nasopharyngeal carcinoma treated with endoscopic nasopharyngectomy plus chemoradiotherapy or with chemoradiotherapy alone: a retrospective study
Background Local residual and recurrent nasopharyngeal carcinoma (NPC) generally shows treatment failure after standard radiotherapy with or without concurrent chemotherapy. Whether endoscopic nasopharyngectomy might provide an additional therapeutic advantage remains controversial. Therefore, we retrospectively compared the clinical prognoses of patients with residual or recurrent NPC treated with endoscopic nasopharyngectomy combined with chemoradiotherapy (CRT) with those of patients treated with CRT alone. Methods and Materials A total of sixty-two patients with local residual or recurrent NPC were studied retrospectively: 36 patients received endoscopic nasopharyngectomy combined with CRT, whereas 26 patients who refused the surgery or had surgical contraindications received CRT alone. Serum Epstein-Barr virus (EBV) DNA levels were measured pre- and post-treatment. The differences in prognosis between the two treatment regimens and the pre- and post-treatment changes in EBV-DNA levels were analyzed. Results The median follow-up time was 31 months, with a 3-year overall survival (OS) of 51.40% and a 3-year disease-free survival (DFS) of 46.86%. The surgery + CRT group had a better OS than the CRT alone group did (χ2 = 4.054, P = 0.044). The pretreatment EBV-DNA levels showed a positive correlation with the clinical staging of recurrent NPC (χ2 = 11.674, P = 0.009). Patients with negative pretreatment serum EBV-DNA levels showed a superior OS to those of patients who tested positive for EBV-DNA (>0 copy/mL) (χ2 = 9.833, P = 0.002). The post-treatment EBV-DNA levels, compared with the pretreatment levels, decreased significantly in the surgery + CRT group (Z = − 3.484, P = 0.000). In contrast, the EBV-DNA levels after CRT alone did not decrease significantly (Z = − 1.956, P = 0.051). Multivariate analysis indicated that local staging, pretreatment EBV-DNA load, and the treatment method were independent risk factors for OS. Subgroup analysis indicated that the patients who tested negative for EBV-DNA before the treatment and those who received surgery + CRT showed a better OS than those who received CRT alone. Conclusions The pretreatment serum EBV-DNA level was associated with disease prognosis. The combination therapy preceded by surgery can effectively decrease the copy number of EBV-DNA. Patients with local intermediate- and late-stage NPC, especially those negative for EBV-DNA, may consider opting for surgery followed by post-operative adjuvant radiotherapy or chemotherapy.
Weng et al. (2017) Clinical outcomes of residual or recurrent nasopharyngeal carcinoma treated with endoscopic nasopharyngectomy plus chemoradiotherapy or with chemoradiotherapy alone: a retrospective study. PeerJ 5:e3912 https://doi.org/10.7717/peerj.3912
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