PeerJ
type: channel
link: https://peerj.com/articles/
description: Articles published in PeerJ
publisher: PeerJ Inc.
publication name: PeerJ
issn: 2167-8359
items: The complete chloroplast genome of Colobanthus apetalus (Labill.) Druce: genome organization and comparison with related species
items: Giant worms chez moi! Hammerhead flatworms (Platyhelminthes, Geoplanidae, Bipalium spp., Diversibipalium spp.) in metropolitan France and overseas French territories
items: Molecular response of canola to salt stress: insights on tolerance mechanisms
items: Identifying potentially marker symptoms of attention-deficit/hyperactivity disorder
items: Effect of Reactive Black 5 azo dye on soil processes related to C and N cycling
items: Influence of aprepitant on the pharmacodynamics and pharmacokinetics of gliclazide in rats and rabbits
items: Large mammal burrows in late Miocene calcic paleosols from central Argentina: paleoenvironment, taphonomy and producers
items: Potentially inappropriate use of benzodiazepines and z-drugs in the older population—analysis of associations between long-term use and patient-related factors
items: Impact of input data (in)accuracy on overestimation of visible area in digital viewshed models
items: On the efficiency of the genetic code after frameshift mutations

The complete chloroplast genome of Colobanthus apetalus (Labill.) Druce: genome organization and comparison with related species
type: item
type: AcademicArticle
description: Colobanthus apetalus is a member of the genus Colobanthus, one of the 86 genera of the large family Caryophyllaceae which groups annual and perennial herbs (rarely shrubs) that are widely distributed around the globe, mainly in the Holarctic. The genus Colobanthus consists of 25 species, including Colobanthus quitensis, an extremophile plant native to the maritime Antarctic. Complete chloroplast (cp) genomes are useful for phylogenetic studies and species identification. In this study, next-generation sequencing (NGS) was used to identify the cp genome of C. apetalus. The complete cp genome of C. apetalus has the length of 151,228 bp, 36.65% GC content, and a quadripartite structure with a large single copy (LSC) of 83,380 bp and a small single copy (SSC) of 17,206 bp separated by inverted repeats (IRs) of 25,321 bp. The cp genome contains 131 genes, including 112 unique genes and 19 genes which are duplicated in the IRs. The group of 112 unique genes features 73 protein-coding genes, 30 tRNA genes, four rRNA genes and five conserved chloroplast open reading frames (ORFs). A total of 12 forward repeats, 10 palindromic repeats, five reverse repeats and three complementary repeats were detected. In addition, a simple sequence repeat (SSR) analysis revealed 41 (mono-, di-, tri-, tetra-, penta- and hexanucleotide) SSRs, most of which were AT-rich. A detailed comparison of C. apetalus and C. quitensis cp genomes revealed identical gene content and order. A phylogenetic tree was built based on the sequences of 76 protein-coding genes that are shared by the eleven sequenced representatives of Caryophyllaceae and C. apetalus, and it revealed that C. apetalus and C. quitensis form a clade that is closely related to Silene species and Agrostemma githago. Moreover, the genus Silene appeared as a polymorphic taxon. The results of this study expand our knowledge about the evolution and molecular biology of Caryophyllaceae.
format: application/pdf
format: text/html
creator: Piotr Androsiuk
creator: Jan Paweł Jastrzębski
creator: Łukasz Paukszto
creator: Adam Okorski
creator: Agnieszka Pszczółkowska
creator: Katarzyna Joanna Chwedorzewska
creator: Justyna Koc
creator: Ryszard Górecki
creator: Irena Giełwanowska
subject: Biodiversity
subject: Bioinformatics
subject: Genetics
subject: Genomics
subject: Plant Science
description: doi:10.7717/peerj.4723
publisher: PeerJ Inc.
rights: © 2018 Androsiuk et al.
abstract: Colobanthus apetalus is a member of the genus Colobanthus, one of the 86 genera of the large family Caryophyllaceae which groups annual and perennial herbs (rarely shrubs) that are widely distributed around the globe, mainly in the Holarctic. The genus Colobanthus consists of 25 species, including Colobanthus quitensis, an extremophile plant native to the maritime Antarctic. Complete chloroplast (cp) genomes are useful for phylogenetic studies and species identification. In this study, next-generation sequencing (NGS) was used to identify the cp genome of C. apetalus. The complete cp genome of C. apetalus has the length of 151,228 bp, 36.65% GC content, and a quadripartite structure with a large single copy (LSC) of 83,380 bp and a small single copy (SSC) of 17,206 bp separated by inverted repeats (IRs) of 25,321 bp. The cp genome contains 131 genes, including 112 unique genes and 19 genes which are duplicated in the IRs. The group of 112 unique genes features 73 protein-coding genes, 30 tRNA genes, four rRNA genes and five conserved chloroplast open reading frames (ORFs). A total of 12 forward repeats, 10 palindromic repeats, five reverse repeats and three complementary repeats were detected. In addition, a simple sequence repeat (SSR) analysis revealed 41 (mono-, di-, tri-, tetra-, penta- and hexanucleotide) SSRs, most of which were AT-rich. A detailed comparison of C. apetalus and C. quitensis cp genomes revealed identical gene content and order. A phylogenetic tree was built based on the sequences of 76 protein-coding genes that are shared by the eleven sequenced representatives of Caryophyllaceae and C. apetalus, and it revealed that C. apetalus and C. quitensis form a clade that is closely related to Silene species and Agrostemma githago. Moreover, the genus Silene appeared as a polymorphic taxon. The results of this study expand our knowledge about the evolution and molecular biology of Caryophyllaceae.
bibliographic citation: Androsiuk et al. (2018) The complete chloroplast genome of Colobanthus apetalus (Labill.) Druce: genome organization and comparison with related species. PeerJ 6:e4723 https://doi.org/10.7717/peerj.4723
date submitted: 2018-01-04
date accepted: 2018-04-17
issued: 2018-05-23
is part of: PeerJ
license: http://creativecommons.org/licenses/by/4.0/
author list: Agent
  family name: Androsiuk
  given name: Piotr
author list: Agent
  family name: Jastrzębski
  given name: Jan Paweł
author list: Agent
  family name: Paukszto
  given name: Łukasz
author list: Agent
  family name: Okorski
  given name: Adam
author list: Agent
  family name: Pszczółkowska
  given name: Agnieszka
author list: Agent
  family name: Chwedorzewska
  given name: Katarzyna Joanna
author list: Agent
  family name: Koc
  given name: Justyna
author list: Agent
  family name: Górecki
  given name: Ryszard
author list: Agent
  family name: Giełwanowska
  given name: Irena
doi: 10.7717/peerj.4723
volume: 6
issn: 2167-8359
publication name: PeerJ
publication date: 2018-05-23
copyright: ©2018 Androsiuk et al.
attribution name: Androsiuk et al.

Giant worms chez moi! Hammerhead flatworms (Platyhelminthes, Geoplanidae, Bipalium spp., Diversibipalium spp.) in metropolitan France and overseas French territories
type: item
type: AcademicArticle
description: Background Species of the genera Bipalium and Diversibipalium, or bipaliines, are giants among land planarians (family Geoplanidae), reaching length of 1 m; they are also easily distinguished from other land flatworms by the characteristic hammer shape of their head. Bipaliines, which have their origin in warm parts of Asia, are invasive species, now widespread worldwide. However, the scientific literature is very scarce about the widespread repartition of these species, and their invasion in European countries has not been studied. Methods In this paper, on the basis of a four year survey based on citizen science, which yielded observations from 1999 to 2017 and a total of 111 records, we provide information about the five species present in Metropolitan France and French overseas territories. We also investigated the molecular variability of cytochrome-oxidase 1 (COI) sequences of specimens. Results Three species are reported from Metropolitan France: Bipalium kewense, Diversibipalium multilineatum, and an unnamed Diversibipalium ‘black’ species. We also report the presence of B. kewense from overseas territories, such as French Polynesia (Oceania), French Guiana (South America), the Caribbean French islands of Martinique, Guadeloupe, Saint Martin and Saint Barthélemy, and Montserrat (Central America), and La Réunion island (off South-East Africa). For B. vagum, observations include French Guiana, Guadeloupe, Martinique, Saint Barthélemy, Saint Martin, Montserrat, La Réunion, and Florida (USA). A probable new species, Diversibipalium sp. ‘blue,’ is reported from Mayotte Island (off South–East Africa). B. kewense, B. vagum and D. multilineatum each showed 0% variability in their COI sequences, whatever their origin, suggesting that the specimens are clonal, and that sexual reproduction is probably absent. COI barcoding was efficient in identifying species, with differences over 10% between species; this suggests that barcoding can be used in the future for identify…
format: application/pdf
format: text/html
creator: Jean-Lou Justine
creator: Leigh Winsor
creator: Delphine Gey
creator: Pierre Gros
creator: Jessica Thévenot
subject: Agricultural Science
subject: Biodiversity
subject: Biogeography
subject: Taxonomy
subject: Zoology
description: doi:10.7717/peerj.4672
publisher: PeerJ Inc.
rights: © 2018 Justine et al.
abstract: Background Species of the genera Bipalium and Diversibipalium, or bipaliines, are giants among land planarians (family Geoplanidae), reaching length of 1 m; they are also easily distinguished from other land flatworms by the characteristic hammer shape of their head. Bipaliines, which have their origin in warm parts of Asia, are invasive species, now widespread worldwide. However, the scientific literature is very scarce about the widespread repartition of these species, and their invasion in European countries has not been studied. Methods In this paper, on the basis of a four year survey based on citizen science, which yielded observations from 1999 to 2017 and a total of 111 records, we provide information about the five species present in Metropolitan France and French overseas territories. We also investigated the molecular variability of cytochrome-oxidase 1 (COI) sequences of specimens. Results Three species are reported from Metropolitan France: Bipalium kewense, Diversibipalium multilineatum, and an unnamed Diversibipalium ‘black’ species. We also report the presence of B. kewense from overseas territories, such as French Polynesia (Oceania), French Guiana (South America), the Caribbean French islands of Martinique, Guadeloupe, Saint Martin and Saint Barthélemy, and Montserrat (Central America), and La Réunion island (off South-East Africa). For B. vagum, observations include French Guiana, Guadeloupe, Martinique, Saint Barthélemy, Saint Martin, Montserrat, La Réunion, and Florida (USA). A probable new species, Diversibipalium sp. ‘blue,’ is reported from Mayotte Island (off South–East Africa). B. kewense, B. vagum and D. multilineatum each showed 0% variability in their COI sequences, whatever their origin, suggesting that the specimens are clonal, and that sexual reproduction is probably absent. COI barcoding was efficient in identifying species, with differences over 10% between species; this suggests that barcoding can be used in the future for identify…
bibliographic citation: Justine et al. (2018) Giant worms chez moi! Hammerhead flatworms (Platyhelminthes, Geoplanidae, Bipalium spp., Diversibipalium spp.) in metropolitan France and overseas French territories. PeerJ 6:e4672 https://doi.org/10.7717/peerj.4672
date submitted: 2017-11-16
date accepted: 2018-04-06
issued: 2018-05-22
is part of: PeerJ
license: http://creativecommons.org/licenses/by/4.0/
author list: Agent
  family name: Justine
  given name: Jean-Lou
author list: Agent
  family name: Winsor
  given name: Leigh
author list: Agent
  family name: Gey
  given name: Delphine
author list: Agent
  family name: Gros
  given name: Pierre
author list: Agent
  family name: Thévenot
  given name: Jessica
doi: 10.7717/peerj.4672
volume: 6
issn: 2167-8359
publication name: PeerJ
publication date: 2018-05-22
copyright: © 2018 Justine et al.
attribution name: Justine et al.

Molecular response of canola to salt stress: insights on tolerance mechanisms
type: item
type: AcademicArticle
description: Canola (Brassica napus L.) is widely cultivated around the world for the production of edible oils and biodiesel fuel. Despite many canola varieties being described as ‘salt-tolerant’, plant yield and growth decline drastically with increasing salinity. Although many studies have resulted in better understanding of the many important salt-response mechanisms that control salt signaling in plants, detoxification of ions, and synthesis of protective metabolites, the engineering of salt-tolerant crops has only progressed slowly. Genetic engineering has been considered as an efficient method for improving the salt tolerance of canola but there are many unknown or little-known aspects regarding canola response to salinity stress at the cellular and molecular level. In order to develop highly salt-tolerant canola, it is essential to improve knowledge of the salt-tolerance mechanisms, especially the key components of the plant salt-response network. In this review, we focus on studies of the molecular response of canola to salinity to unravel the different pieces of the salt response puzzle. The paper includes a comprehensive review of the latest studies, particularly of proteomic and transcriptomic analysis, including the most recently identified canola tolerance components under salt stress, and suggests what researchers should focus on in future studies.
format: application/pdf
format: text/html
creator: Reza Shokri-Gharelo
creator: Pouya Motie Noparvar
subject: Agricultural Science
subject: Cell Biology
subject: Molecular Biology
subject: Plant Science
description: doi:10.7717/peerj.4822
publisher: PeerJ Inc.
rights: © 2018 Shokri-Gharelo and Noparvar
abstract: Canola (Brassica napus L.) is widely cultivated around the world for the production of edible oils and biodiesel fuel. Despite many canola varieties being described as ‘salt-tolerant’, plant yield and growth decline drastically with increasing salinity. Although many studies have resulted in better understanding of the many important salt-response mechanisms that control salt signaling in plants, detoxification of ions, and synthesis of protective metabolites, the engineering of salt-tolerant crops has only progressed slowly. Genetic engineering has been considered as an efficient method for improving the salt tolerance of canola but there are many unknown or little-known aspects regarding canola response to salinity stress at the cellular and molecular level. In order to develop highly salt-tolerant canola, it is essential to improve knowledge of the salt-tolerance mechanisms, especially the key components of the plant salt-response network. In this review, we focus on studies of the molecular response of canola to salinity to unravel the different pieces of the salt response puzzle. The paper includes a comprehensive review of the latest studies, particularly of proteomic and transcriptomic analysis, including the most recently identified canola tolerance components under salt stress, and suggests what researchers should focus on in future studies.
bibliographic citation: Shokri-Gharelo et al. (2018) Molecular response of canola to salt stress: insights on tolerance mechanisms. PeerJ 6:e4822 https://doi.org/10.7717/peerj.4822
date submitted: 2018-03-09
date accepted: 2018-05-02
issued: 2018-05-22
is part of: PeerJ
license: http://creativecommons.org/licenses/by/4.0/
author list: Agent
  family name: Shokri-Gharelo
  given name: Reza
author list: Agent
  family name: Noparvar
  given name: Pouya Motie
doi: 10.7717/peerj.4822
volume: 6
issn: 2167-8359
publication name: PeerJ
publication date: 2018-05-22
copyright: ©2018 Shokri-Gharelo and Noparvar
attribution name: Shokri-Gharelo and Noparvar

Identifying potentially marker symptoms of attention-deficit/hyperactivity disorder
type: item
type: AcademicArticle
description: Background For the diagnosis of attention-deficit/hyperactivity disorder (ADHD), the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) proposes that adherence to six symptoms in either group (inattention and hyperactivity/impulsivity) will lead to the diagnosis of one of three presentations of the disorder. Underlying this diagnostic algorithm is the assumption that the 18 symptoms have equal relevance for the diagnosis of ADHD, all are equally severe, and all have the same power to detect the presence of the disorder in all its degrees of severity, without considering the possibility of using marker symptoms. However, several studies have suggested that ADHD symptoms differ in both their power to discriminate the presence of the disorder and the degree of severity they represent. The aim of the present study was to replicate the results of previous research by evaluating the discriminative capacity and relative severity of ADHD symptoms, as well as to extend the investigation of this topic to Spanish-speaking Latin American samples. Methods The properties of ADHD symptoms rated by the parents of 474 Chilean children were analyzed. Symptom parameters were estimated using the graded response model. Results The results suggest that symptoms of ADHD differ substantially in both the accuracy with which they reflect the presence of the disorder, and their relative severity. Symptoms “easily distracted by extraneous stimuli” and “have difficulty sustaining attention in tasks” (inattention) and “is on the go, acting as if driven by motor” (hyperactivity/impulsivity) were the most informative, and those with relatively lower severity thresholds. Discussion The fact that symptoms differ substantially in the probability of being observed conditionally to the trait level suggests the need to refine the diagnostic process by weighting the severity of the symptom, and even to assess the possibility of defining ADHD marker symptoms, as has been done in other disorders…
format: application/pdf
format: text/html
creator: Víctor B. Arias
creator: Igor Esnaola
creator: Jairo Rodríguez-Medina
subject: Psychiatry and Psychology
subject: Statistics
description: doi:10.7717/peerj.4820
publisher: PeerJ Inc.
rights: © 2018 Arias et al.
abstract: Background For the diagnosis of attention-deficit/hyperactivity disorder (ADHD), the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) proposes that adherence to six symptoms in either group (inattention and hyperactivity/impulsivity) will lead to the diagnosis of one of three presentations of the disorder. Underlying this diagnostic algorithm is the assumption that the 18 symptoms have equal relevance for the diagnosis of ADHD, all are equally severe, and all have the same power to detect the presence of the disorder in all its degrees of severity, without considering the possibility of using marker symptoms. However, several studies have suggested that ADHD symptoms differ in both their power to discriminate the presence of the disorder and the degree of severity they represent. The aim of the present study was to replicate the results of previous research by evaluating the discriminative capacity and relative severity of ADHD symptoms, as well as to extend the investigation of this topic to Spanish-speaking Latin American samples. Methods The properties of ADHD symptoms rated by the parents of 474 Chilean children were analyzed. Symptom parameters were estimated using the graded response model. Results The results suggest that symptoms of ADHD differ substantially in both the accuracy with which they reflect the presence of the disorder, and their relative severity. Symptoms “easily distracted by extraneous stimuli” and “have difficulty sustaining attention in tasks” (inattention) and “is on the go, acting as if driven by motor” (hyperactivity/impulsivity) were the most informative, and those with relatively lower severity thresholds. Discussion The fact that symptoms differ substantially in the probability of being observed conditionally to the trait level suggests the need to refine the diagnostic process by weighting the severity of the symptom, and even to assess the possibility of defining ADHD marker symptoms, as has been done in other disorders…
bibliographic citation: Arias et al. (2018) Identifying potentially marker symptoms of attention-deficit/hyperactivity disorder. PeerJ 6:e4820 https://doi.org/10.7717/peerj.4820
date submitted: 2018-03-10
date accepted: 2018-05-02
issued: 2018-05-22
is part of: PeerJ
license: http://creativecommons.org/licenses/by/4.0/
author list: Agent
  family name: Arias
  given name: Víctor B.
author list: Agent
  family name: Esnaola
  given name: Igor
author list: Agent
  family name: Rodríguez-Medina
  given name: Jairo
doi: 10.7717/peerj.4820
volume: 6
issn: 2167-8359
publication name: PeerJ
publication date: 2018-05-22
copyright: ©2018 Arias et al.
attribution name: Arias et al.

Effect of Reactive Black 5 azo dye on soil processes related to C and N cycling
type: item
type: AcademicArticle
description: Azo dyes are one of the largest classes of synthetic dyes being used in textile industries. It has been reported that 15–50% of these dyes find their way into wastewater that is often used for irrigation purpose in developing countries. The effect of azo dyes contamination on soil nitrogen (N) has been studied previously. However, how does the azo dye contamination affect soil carbon (C) cycling is unknown. Therefore, we assessed the effect of azo dye contamination (Reactive Black 5, 30 mg kg−1 dry soil), bacteria that decolorize this dye and dye + bacteria in the presence or absence of maize leaf litter on soil respiration, soil inorganic N and microbial biomass. We found that dye contamination did not induce any change in soil respiration, soil microbial biomass or soil inorganic N availability (P > 0.05). Litter evidently increased soil respiration. Our study concludes that the Reactive Black 5 azo dye (applied in low amount, i.e., 30 mg kg−1 dry soil) contamination did not modify organic matter decomposition, N mineralization and microbial biomass in a silty loam soil.
format: application/pdf
format: text/html
creator: Khadeeja Rehman
creator: Tanvir Shahzad
creator: Amna Sahar
creator: Sabir Hussain
creator: Faisal Mahmood
creator: Muhammad H. Siddique
creator: Muhammad A. Siddique
creator: Muhammad I. Rashid
subject: Soil Science
subject: Environmental Impacts
description: doi:10.7717/peerj.4802
publisher: PeerJ Inc.
rights: © 2018 Rehman et al.
abstract: Azo dyes are one of the largest classes of synthetic dyes being used in textile industries. It has been reported that 15–50% of these dyes find their way into wastewater that is often used for irrigation purpose in developing countries. The effect of azo dyes contamination on soil nitrogen (N) has been studied previously. However, how does the azo dye contamination affect soil carbon (C) cycling is unknown. Therefore, we assessed the effect of azo dye contamination (Reactive Black 5, 30 mg kg−1 dry soil), bacteria that decolorize this dye and dye + bacteria in the presence or absence of maize leaf litter on soil respiration, soil inorganic N and microbial biomass. We found that dye contamination did not induce any change in soil respiration, soil microbial biomass or soil inorganic N availability (P > 0.05). Litter evidently increased soil respiration. Our study concludes that the Reactive Black 5 azo dye (applied in low amount, i.e., 30 mg kg−1 dry soil) contamination did not modify organic matter decomposition, N mineralization and microbial biomass in a silty loam soil.
bibliographic citation: Rehman et al. (2018) Effect of Reactive Black 5 azo dye on soil processes related to C and N cycling. PeerJ 6:e4802 https://doi.org/10.7717/peerj.4802
date submitted: 2018-02-21
date accepted: 2018-04-30
issued: 2018-05-22
is part of: PeerJ
license: http://creativecommons.org/licenses/by/4.0/
author list: Agent
  family name: Rehman
  given name: Khadeeja
author list: Agent
  family name: Shahzad
  given name: Tanvir
author list: Agent
  family name: Sahar
  given name: Amna
author list: Agent
  family name: Hussain
  given name: Sabir
author list: Agent
  family name: Mahmood
  given name: Faisal
author list: Agent
  family name: Siddique
  given name: Muhammad H.
author list: Agent
  family name: Siddique
  given name: Muhammad A.
author list: Agent
  family name: Rashid
  given name: Muhammad I.
doi: 10.7717/peerj.4802
volume: 6
issn: 2167-8359
publication name: PeerJ
publication date: 2018-05-22
copyright: ©2018 Rehman et al.
attribution name: Rehman et al.

Influence of aprepitant on the pharmacodynamics and pharmacokinetics of gliclazide in rats and rabbits
type: item
type: AcademicArticle
description: Background Concomitant drug administration is a general phenomenon in patients with chronic diseases such as diabetes mellitus. Among the currently available oral antidiabetic drugs, gliclazide is a commonly prescribed drug considering its multiple benefits in diabetic patients. Aprepitant is a commonly prescribed antiemetic drug which is mainly metabolized by CYP3A4, reported to have modest inductive and inhibitory effects on CYP2C9 and CYP3A4, respectively. Since gliclazide is metabolized by CYP2C9 (major) and CYP3A4 (minor), it is very difficult to predict the influence of aprepitant and its metabolic interaction with gliclazide. Considering the complexity associated with the combination of aprepitant and gliclazide, this study was designed to evaluate the influence of aprepitant on the pharmacodynamics (PD) and pharmacokinetics (PK) of gliclazide in animal models. Methods The PD interaction studies were conducted in both rodent (normal and alloxan-induced diabetic rats) and non-rodent (rabbits) animal models (n = 6) while the PK interaction study was conducted in normal rabbits (n = 6). An extrapolated human therapeutic oral dose of gliclazide, aprepitant and their combination were administered to rats and rabbits with 7 days washout between each treatment. For the multiple-dose interaction study, the same groups were administered with an interacting drug (aprepitant) for 7 days and then the combination of aprepitant and gliclazide on the 8th day. From the collected animal blood samples, blood glucose (by Glucose-Oxidase/Peroxidase method), insulin (by ELISA method) and gliclazide concentration levels (by HPLC method) were determined. Non-compartmental PK analysis was conducted by Phoenix WinNonlin software to determine the PK parameters of gliclazide. Statistical analysis was performed by student’s paired t-test. Results The pharmacodynamic activity (blood glucose reduction and insulin levels) of gliclazide was significantly (p < 0.05) influenced by aprepitant …
format: application/pdf
format: text/html
creator: Raghunandan Reddy Kura
creator: Eswar Kumar Kilari
creator: Mastan Shaik
subject: Diabetes and Endocrinology
subject: Pharmacology
description: doi:10.7717/peerj.4798
publisher: PeerJ Inc.
rights: © 2018 Kura et al.
abstract: Background Concomitant drug administration is a general phenomenon in patients with chronic diseases such as diabetes mellitus. Among the currently available oral antidiabetic drugs, gliclazide is a commonly prescribed drug considering its multiple benefits in diabetic patients. Aprepitant is a commonly prescribed antiemetic drug which is mainly metabolized by CYP3A4, reported to have modest inductive and inhibitory effects on CYP2C9 and CYP3A4, respectively. Since gliclazide is metabolized by CYP2C9 (major) and CYP3A4 (minor), it is very difficult to predict the influence of aprepitant and its metabolic interaction with gliclazide. Considering the complexity associated with the combination of aprepitant and gliclazide, this study was designed to evaluate the influence of aprepitant on the pharmacodynamics (PD) and pharmacokinetics (PK) of gliclazide in animal models. Methods The PD interaction studies were conducted in both rodent (normal and alloxan-induced diabetic rats) and non-rodent (rabbits) animal models (n = 6) while the PK interaction study was conducted in normal rabbits (n = 6). An extrapolated human therapeutic oral dose of gliclazide, aprepitant and their combination were administered to rats and rabbits with 7 days washout between each treatment. For the multiple-dose interaction study, the same groups were administered with an interacting drug (aprepitant) for 7 days and then the combination of aprepitant and gliclazide on the 8th day. From the collected animal blood samples, blood glucose (by Glucose-Oxidase/Peroxidase method), insulin (by ELISA method) and gliclazide concentration levels (by HPLC method) were determined. Non-compartmental PK analysis was conducted by Phoenix WinNonlin software to determine the PK parameters of gliclazide. Statistical analysis was performed by student’s paired t-test. Results The pharmacodynamic activity (blood glucose reduction and insulin levels) of gliclazide was significantly (p < 0.05) influenced by aprepitant …
bibliographic citation: Kura et al. (2018) Influence of aprepitant on the pharmacodynamics and pharmacokinetics of gliclazide in rats and rabbits. PeerJ 6:e4798 https://doi.org/10.7717/peerj.4798
date submitted: 2018-02-23
date accepted: 2018-04-30
issued: 2018-05-22
is part of: PeerJ
license: http://creativecommons.org/licenses/by/4.0/
author list: Agent
  family name: Kura
  given name: Raghunandan Reddy
author list: Agent
  family name: Kilari
  given name: Eswar Kumar
author list: Agent
  family name: Shaik
  given name: Mastan
doi: 10.7717/peerj.4798
volume: 6
issn: 2167-8359
publication name: PeerJ
publication date: 2018-05-22
copyright: ©2018 Kura et al.
attribution name: Kura et al.

Large mammal burrows in late Miocene calcic paleosols from central Argentina: paleoenvironment, taphonomy and producers
type: item
type: AcademicArticle
description: Large cylindrical sediment-filled structures interpreted as mammal burrows occur within the loess-paleosol sequence of the late Miocene Cerro Azul Formation of central Argentina. A total of 115 burrow fills from three localities were measured. They are typically shallowly dipping, subcylindrical, unbranched structures with rounded ends and lacking enlargements. The horizontal diameter of the burrows range between 0.15 and 1.50 m, with most of the burrows in the interval of 0.39 to 0.98 m. Geometric morphometric analysis of transverse cross-sections support their distinct subcircular and elliptical (horizontally flattened) shapes. Burrow fills are typically laminated in the lower part and massive in the upper part. The laminated intervals reflect pulses of flowing water entering the abandoned burrow during moderate rains, whereas massive intervals reflect mass flow input of dense sediment-water mixtures during heavy rains that produced sheet floods. Approximately 1% of the burrows contained fragmentary, disarticulated and weathered mammal bones that were introduced in the open burrow by currents along with other sedimentary particles. Analysis of the tetrapod burrow fossil record suggests that Miocene burrows, including those studied herein, reflect a remarkable increase in the average size of the fossorial fauna. We conclude that large late Miocene mammals dug burrows essentially as a shelter against environmental extremes and to escape predation. The simple architecture of the burrows suggests that the producers essentially foraged aboveground. Several mammal groups acquired fossorial habits in response to cold and seasonally dry climatic conditions that prevailed during the late Miocene in southern South America. The considerable range of horizontal diameters of the studied burrows can be attributed to a variety of producers, including dasypodids, the notoungulate Paedotherium minor, Glyptodontidae and Proscelidodon sp.
format: application/pdf
format: text/html
creator: María Cristina Cardonatto
creator: Ricardo Néstor Melchor
subject: Animal Behavior
subject: Paleontology
description: doi:10.7717/peerj.4787
publisher: PeerJ Inc.
rights: © 2018 Cardonatto and Melchor
abstract: Large cylindrical sediment-filled structures interpreted as mammal burrows occur within the loess-paleosol sequence of the late Miocene Cerro Azul Formation of central Argentina. A total of 115 burrow fills from three localities were measured. They are typically shallowly dipping, subcylindrical, unbranched structures with rounded ends and lacking enlargements. The horizontal diameter of the burrows range between 0.15 and 1.50 m, with most of the burrows in the interval of 0.39 to 0.98 m. Geometric morphometric analysis of transverse cross-sections support their distinct subcircular and elliptical (horizontally flattened) shapes. Burrow fills are typically laminated in the lower part and massive in the upper part. The laminated intervals reflect pulses of flowing water entering the abandoned burrow during moderate rains, whereas massive intervals reflect mass flow input of dense sediment-water mixtures during heavy rains that produced sheet floods. Approximately 1% of the burrows contained fragmentary, disarticulated and weathered mammal bones that were introduced in the open burrow by currents along with other sedimentary particles. Analysis of the tetrapod burrow fossil record suggests that Miocene burrows, including those studied herein, reflect a remarkable increase in the average size of the fossorial fauna. We conclude that large late Miocene mammals dug burrows essentially as a shelter against environmental extremes and to escape predation. The simple architecture of the burrows suggests that the producers essentially foraged aboveground. Several mammal groups acquired fossorial habits in response to cold and seasonally dry climatic conditions that prevailed during the late Miocene in southern South America. The considerable range of horizontal diameters of the studied burrows can be attributed to a variety of producers, including dasypodids, the notoungulate Paedotherium minor, Glyptodontidae and Proscelidodon sp.
bibliographic citation: Cardonatto et al. (2018) Large mammal burrows in late Miocene calcic paleosols from central Argentina: paleoenvironment, taphonomy and producers. PeerJ 6:e4787 https://doi.org/10.7717/peerj.4787
date submitted: 2018-03-05
date accepted: 2018-04-27
issued: 2018-05-22
is part of: PeerJ
license: http://creativecommons.org/licenses/by/4.0/
author list: Agent
  family name: Cardonatto
  given name: María Cristina
author list: Agent
  family name: Melchor
  given name: Ricardo Néstor
doi: 10.7717/peerj.4787
volume: 6
issn: 2167-8359
publication name: PeerJ
publication date: 2018-05-22
copyright: ©2018 Cardonatto and Melchor
attribution name: Cardonatto and Melchor

Potentially inappropriate use of benzodiazepines and z-drugs in the older population—analysis of associations between long-term use and patient-related factors
type: item
type: AcademicArticle
description: Introduction The long-term use of benzodiazepines (BZD) and z-drugs in older populations is associated with a variety of sociodemographic and health-related factors. Recent studies reported that long-term BZD and z-drugs use is associated with increased age, female sex, and severe negative psychological (e.g., depression) and somatic (e.g., chronic disease) factors. The current study explores the sociodemographic and health-related factors associated with long-term BZD and z-drugs use in the elderly. Methods We conducted a cross-sectional survey among randomly selected patients of one health insurance plan (“AOK North-West”) with BZD and z-drugs prescriptions in the past 12 months. The sample was stratified by appropriate German prescription guidelines (yes vs. no) and age (50–65 vs. >65 years). To examine the association of selected sociodemographic and psychological variables (e.g., sex, employment status, quality of life, depression) with long-term use, a binary logistic regression analysis was conducted. Results In total, data from 340 patients were analyzed. The mean age was 72.1 (SD = 14.5) years, and the most commonly used substances were zopiclon (38.1%), oxazepam (18.1%), and lorazepam (13.8%). The mean defined daily dose (DDD) was 0.73 (SD = 0.47). Insomnia was the main reason for prescribing BZD and z-drugs. The long-term use of BZD and z-drugs was significantly associated with unemployment (OR = 2.9, 95% CI [1.2–7.1]) and generally problematic medication use (OR = 0.5, 95% CI [0.2–1.0]). Discussion Unemployment status and problematic medication use had a significant association with the patient-reported, long-term use of BZD and z-drugs. Divergent prescription patterns might suggest problematic patterns of BZD and z-drugs use. The causal connection between the identified factors and problematic BZD and z-drugs prescription is not discussed in this paper. Nevertheless, employment status and possible evidence of general problematic drug use may be a warnin…
format: application/pdf
format: text/html
creator: Aliaksandra Mokhar
creator: Niklas Tillenburg
creator: Jörg Dirmaier
creator: Silke Kuhn
creator: Martin Härter
creator: Uwe Verthein
subject: Geriatrics
subject: Pharmacology
subject: Psychiatry and Psychology
subject: Public Health
description: doi:10.7717/peerj.4614
publisher: PeerJ Inc.
rights: © 2018 Mokhar et al.
abstract: Introduction The long-term use of benzodiazepines (BZD) and z-drugs in older populations is associated with a variety of sociodemographic and health-related factors. Recent studies reported that long-term BZD and z-drugs use is associated with increased age, female sex, and severe negative psychological (e.g., depression) and somatic (e.g., chronic disease) factors. The current study explores the sociodemographic and health-related factors associated with long-term BZD and z-drugs use in the elderly. Methods We conducted a cross-sectional survey among randomly selected patients of one health insurance plan (“AOK North-West”) with BZD and z-drugs prescriptions in the past 12 months. The sample was stratified by appropriate German prescription guidelines (yes vs. no) and age (50–65 vs. >65 years). To examine the association of selected sociodemographic and psychological variables (e.g., sex, employment status, quality of life, depression) with long-term use, a binary logistic regression analysis was conducted. Results In total, data from 340 patients were analyzed. The mean age was 72.1 (SD = 14.5) years, and the most commonly used substances were zopiclon (38.1%), oxazepam (18.1%), and lorazepam (13.8%). The mean defined daily dose (DDD) was 0.73 (SD = 0.47). Insomnia was the main reason for prescribing BZD and z-drugs. The long-term use of BZD and z-drugs was significantly associated with unemployment (OR = 2.9, 95% CI [1.2–7.1]) and generally problematic medication use (OR = 0.5, 95% CI [0.2–1.0]). Discussion Unemployment status and problematic medication use had a significant association with the patient-reported, long-term use of BZD and z-drugs. Divergent prescription patterns might suggest problematic patterns of BZD and z-drugs use. The causal connection between the identified factors and problematic BZD and z-drugs prescription is not discussed in this paper. Nevertheless, employment status and possible evidence of general problematic drug use may be a warnin…
bibliographic citation: Mokhar et al. (2018) Potentially inappropriate use of benzodiazepines and z-drugs in the older population—analysis of associations between long-term use and patient-related factors. PeerJ 6:e4614 https://doi.org/10.7717/peerj.4614
date submitted: 2017-12-18
date accepted: 2018-03-23
issued: 2018-05-22
is part of: PeerJ
license: http://creativecommons.org/licenses/by/4.0/
author list: Agent
  family name: Mokhar
  given name: Aliaksandra
author list: Agent
  family name: Tillenburg
  given name: Niklas
author list: Agent
  family name: Dirmaier
  given name: Jörg
author list: Agent
  family name: Kuhn
  given name: Silke
author list: Agent
  family name: Härter
  given name: Martin
author list: Agent
  family name: Verthein
  given name: Uwe
doi: 10.7717/peerj.4614
volume: 6
issn: 2167-8359
publication name: PeerJ
publication date: 2018-05-22
copyright: ©2018 Mokhar et al.
attribution name: Mokhar et al.

Impact of input data (in)accuracy on overestimation of visible area in digital viewshed models
type: item
type: AcademicArticle
description: Viewshed analysis is a GIS tool in standard use for more than two decades to perform numerous scientific and practical tasks. The reliability of the resulting viewshed model depends on the computational algorithm and the quality of the input digital surface model (DSM). Although many studies have dealt with improving viewshed algorithms, only a few studies have focused on the effect of the spatial accuracy of input data. Here, we compare simple binary viewshed models based on DSMs having varying levels of detail with viewshed models created using LiDAR DSM. The compared DSMs were calculated as the sums of digital terrain models (DTMs) and layers of forests and buildings with expertly assigned heights. Both elevation data and the visibility obstacle layers were prepared using digital vector maps differing in scale (1:5,000, 1:25,000, and 1:500,000) as well as using a combination of a LiDAR DTM with objects vectorized on an orthophotomap. All analyses were performed for 104 sample locations of 5 km2, covering areas from lowlands to mountains and including farmlands as well as afforested landscapes. We worked with two observer point heights, the first (1.8 m) simulating observation by a person standing on the ground and the second (80 m) as observation from high structures such as wind turbines, and with five estimates of forest heights (15, 20, 25, 30, and 35 m). At all height estimations, all of the vector-based DSMs used resulted in overestimations of visible areas considerably greater than those from the LiDAR DSM. In comparison to the effect from input data scale, the effect from object height estimation was shown to be secondary.
format: application/pdf
format: text/html
creator: Ondřej Lagner
creator: Tomáš Klouček
creator: Petra Šímová
subject: Ecosystem Science
subject: Spatial and Geographic Information Science
description: doi:10.7717/peerj.4835
publisher: PeerJ Inc.
rights: © 2018 Lagner et al.
abstract: Viewshed analysis is a GIS tool in standard use for more than two decades to perform numerous scientific and practical tasks. The reliability of the resulting viewshed model depends on the computational algorithm and the quality of the input digital surface model (DSM). Although many studies have dealt with improving viewshed algorithms, only a few studies have focused on the effect of the spatial accuracy of input data. Here, we compare simple binary viewshed models based on DSMs having varying levels of detail with viewshed models created using LiDAR DSM. The compared DSMs were calculated as the sums of digital terrain models (DTMs) and layers of forests and buildings with expertly assigned heights. Both elevation data and the visibility obstacle layers were prepared using digital vector maps differing in scale (1:5,000, 1:25,000, and 1:500,000) as well as using a combination of a LiDAR DTM with objects vectorized on an orthophotomap. All analyses were performed for 104 sample locations of 5 km2, covering areas from lowlands to mountains and including farmlands as well as afforested landscapes. We worked with two observer point heights, the first (1.8 m) simulating observation by a person standing on the ground and the second (80 m) as observation from high structures such as wind turbines, and with five estimates of forest heights (15, 20, 25, 30, and 35 m). At all height estimations, all of the vector-based DSMs used resulted in overestimations of visible areas considerably greater than those from the LiDAR DSM. In comparison to the effect from input data scale, the effect from object height estimation was shown to be secondary.
bibliographic citation: Lagner et al. (2018) Impact of input data (in)accuracy on overestimation of visible area in digital viewshed models. PeerJ 6:e4835 https://doi.org/10.7717/peerj.4835
date submitted: 2018-02-23
date accepted: 2018-05-03
issued: 2018-05-21
is part of: PeerJ
license: http://creativecommons.org/licenses/by/4.0/
author list: Agent
  family name: Lagner
  given name: Ondřej
author list: Agent
  family name: Klouček
  given name: Tomáš
author list: Agent
  family name: Šímová
  given name: Petra
doi: 10.7717/peerj.4835
volume: 6
issn: 2167-8359
publication name: PeerJ
publication date: 2018-05-21
copyright: ©2018 Lagner et al.
attribution name: Lagner et al.

On the efficiency of the genetic code after frameshift mutations
type: item
type: AcademicArticle
description: Statistical and biochemical studies of the standard genetic code (SGC) have found evidence that the impact of mistranslations is minimized in a way that erroneous codes are either synonymous or code for an amino acid with similar polarity as the originally coded amino acid. It could be quantified that the SGC is optimized to protect this specific chemical property as good as possible. In recent work, it has been speculated that the multilevel optimization of the genetic code stands in the wider context of overlapping codes. This work tries to follow the systematic approach on mistranslations and to extend those analyses to the general effect of frameshift mutations on the polarity conservation of amino acids. We generated one million random codes and compared their average polarity change over all triplets and the whole set of possible frameshift mutations. While the natural code—just as for the point mutations—appears to be competitively robust against frameshift mutations as well, we found that both optimizations appear to be independent of each other. For both, better codes can be found, but it becomes significantly more difficult to find candidates that optimize all of these features—just like the SGC does. We conclude that the SGC is not only very efficient in minimizing the consequences of mistranslations, but rather optimized in amino acid polarity conservation for all three effects of code alteration, namely translational errors, point and frameshift mutations. In other words, our result demonstrates that the SGC appears to be much more than just “one in a million”.
format: application/pdf
format: text/html
creator: Regine Geyer
creator: Amir Madany Mamlouk
subject: Bioinformatics
subject: Evolutionary Studies
subject: Genetics
description: doi:10.7717/peerj.4825
publisher: PeerJ Inc.
rights: © 2018 Geyer and Madany Mamlouk
abstract: Statistical and biochemical studies of the standard genetic code (SGC) have found evidence that the impact of mistranslations is minimized in a way that erroneous codes are either synonymous or code for an amino acid with similar polarity as the originally coded amino acid. It could be quantified that the SGC is optimized to protect this specific chemical property as good as possible. In recent work, it has been speculated that the multilevel optimization of the genetic code stands in the wider context of overlapping codes. This work tries to follow the systematic approach on mistranslations and to extend those analyses to the general effect of frameshift mutations on the polarity conservation of amino acids. We generated one million random codes and compared their average polarity change over all triplets and the whole set of possible frameshift mutations. While the natural code—just as for the point mutations—appears to be competitively robust against frameshift mutations as well, we found that both optimizations appear to be independent of each other. For both, better codes can be found, but it becomes significantly more difficult to find candidates that optimize all of these features—just like the SGC does. We conclude that the SGC is not only very efficient in minimizing the consequences of mistranslations, but rather optimized in amino acid polarity conservation for all three effects of code alteration, namely translational errors, point and frameshift mutations. In other words, our result demonstrates that the SGC appears to be much more than just “one in a million”.
bibliographic citation: Geyer et al. (2018) On the efficiency of the genetic code after frameshift mutations. PeerJ 6:e4825 https://doi.org/10.7717/peerj.4825
date submitted: 2017-10-02
date accepted: 2018-05-02
issued: 2018-05-21
is part of: PeerJ
license: http://creativecommons.org/licenses/by/4.0/
author list: Agent
  family name: Geyer
  given name: Regine
author list: Agent
  family name: Madany Mamlouk
  given name: Amir
doi: 10.7717/peerj.4825
volume: 6
issn: 2167-8359
publication name: PeerJ
publication date: 2018-05-21
copyright: ©2018 Geyer and Madany Mamlouk
attribution name: Geyer and Madany Mamlouk

PeerJ
type: Periodical
uri: PeerJ
issn: 2167-8359