Dopamine and eye movement control in Parkinson’s disease: deficits in corollary discharge signals?
Movement in Parkinson’s disease (PD) is fragmented, and the patients depend on visual information in their behavior. This suggests that the patients may have deficits in internally monitoring their own movements. Internal monitoring of movements is assumed to rely on corollary discharge signals that enable the brain to predict the sensory consequences of actions. We studied early-stage PD patients (N = 14), and age-matched healthy control participants (N = 14) to examine whether PD patients reveal deficits in updating their sensory representations after eye movements. The participants performed a double-saccade task where, in order to accurately fixate a second target, the participant must correct for the displacement caused by the first saccade. In line with previous reports, the patients had difficulties in fixating the second target when the eye movement was performed without visual guidance. Furthermore, the patients had difficulties in taking into account the error in the first saccade when making a saccade toward the second target, especially when eye movements were made toward the side with dominant motor symptoms. Across PD patients, the impairments in saccadic eye movements correlated with the integrity of the dopaminergic system as measured with [123I]FP-CIT SPECT: Patients with lower striatal (caudate, anterior putamen, and posterior putamen) dopamine transporter binding made larger errors in saccades. This effect was strongest when patients made memory-guided saccades toward the second target. Our results provide tentative evidence that the motor deficits in PD may be partly due to deficits in internal monitoring of movements.
Railo et al. (2018) Dopamine and eye movement control in Parkinson’s disease: deficits in corollary discharge signals?. PeerJ 6:e6038 https://doi.org/10.7717/peerj.6038
RIP-MD: a tool to study residue interaction networks in protein molecular dynamics
Protein structure is not static; residues undergo conformational rearrangements and, in doing so, create, stabilize or break non-covalent interactions. Molecular dynamics (MD) is a technique used to simulate these movements with atomic resolution. However, given the data-intensive nature of the technique, gathering relevant information from MD simulations is a complex and time consuming process requiring several computational tools to perform these analyses. Among different approaches, the study of residue interaction networks (RINs) has proven to facilitate the study of protein structures. In a RIN, nodes represent amino-acid residues and the connections between them depict non-covalent interactions. Here, we describe residue interaction networks in protein molecular dynamics (RIP-MD), a visual molecular dynamics (VMD) plugin to facilitate the study of RINs using trajectories obtained from MD simulations of proteins. Our software generates RINs from MD trajectory files. The non-covalent interactions defined by RIP-MD include H-bonds, salt bridges, VdWs, cation-π, π–π, Arginine–Arginine, and Coulomb interactions. In addition, RIP-MD also computes interactions based on distances between Cαs and disulfide bridges. The results of the analysis are shown in an user friendly interface. Moreover, the user can take advantage of the VMD visualization capacities, whereby through some effortless steps, it is possible to select and visualize interactions described for a single, several or all residues in a MD trajectory. Network and descriptive table files are also generated, allowing their further study in other specialized platforms. Our method was written in python in a parallelized fashion. This characteristic allows the analysis of large systems impossible to handle otherwise. RIP-MD is available at http://www.dlab.cl/ripmd.
Contreras-Riquelme et al. (2018) RIP-MD: a tool to study residue interaction networks in protein molecular dynamics. PeerJ 6:e5998 https://doi.org/10.7717/peerj.5998
Bait-attending amphipods of the Tonga Trench and depth-stratified population structure in the scavenging amphipod Hirondellea dubia Dahl, 1959
Background The hadal zone encompasses the deepest parts of the world’s ocean trenches from depths of ∼6,000–11,000 m. The communities observed at these depths are dominated by scavenging amphipods that rapidly intercept and consume carrion as it falls to the deepest parts of the trenches. New samples collected in the Tonga Trench provide an opportunity to compare the amphipod assemblages and the population structure of a dominant species, Hirondellea dubia Dahl, 1959, between trenches and with earlier data presented for the Tonga Trench, and other trenches in the South Pacific. Methods Over 3,600 individual scavenging amphipods across 10 species were collected in seven baited traps at two sites; in the Horizon Deep site, the deepest part of the Tonga Trench (10,800 m) and a site directly up-slope at the trench edge (6,250 m). The composition of the bait-attending amphipods is described and a morphometric analysis of H. dubia examines the bathymetric distribution of the different life stages encountered. Results The amphipod assemblage was more diverse than previously reported, seven species were recorded for the first time from the Tonga Trench. The species diversity was highest at the shallower depth, with H. dubia the only species captured at the deepest site. At the same time, the abundance of amphipods collected at 10,800 m was around sevenfold higher than at the shallower site. H. dubia showed clear ontogenetic vertical structuring, with juveniles dominant at the shallow site and adults dominant at the deep site. The amphipods of the deeper site were always larger at comparable life stage. Discussion The numbers of species encountered in the Tonga Trench is less than reported from the New Hebrides and Kermadec trenches, and six species encountered are shared across trenches. These findings support the previous suggestion that the fauna of the New Hebrides, Tonga and Kermadec Trenches may represent a single biogeographic province. The ontogenetic shift in H. dubia between the two Tonga Trench sites supports the hypothesis of interspecific competition at the shallower bathymetric range of the species, and the presence of competitive physiological advantages that allow the adults at the trench axis to exploit the more labile organic material that reaches the bottom of the trench.
Wilson et al. (2018) Bait-attending amphipods of the Tonga Trench and depth-stratified population structure in the scavenging amphipod Hirondellea dubia Dahl, 1959. PeerJ 6:e5994 https://doi.org/10.7717/peerj.5994
Abstract, emotional and concrete concepts and the activation of mouth-hand effectors
According to embodied and grounded theories, concepts are grounded in sensorimotor systems. The majority of evidence supporting these views concerns concepts referring to objects or actions, while evidence on abstract concepts is more scarce. Explaining how abstract concepts such as “freedom” are represented would thus be pivotal for grounded theories. According to some recent proposals, abstract concepts are grounded in both sensorimotor and linguistic experience, thus they activate the mouth motor system more than concrete concepts. Two experiments are reported, aimed at verifying whether abstract, concrete and emotional words activate the mouth and the hand effectors. In both experiments participants performed first a lexical decision, then a recognition task. In Experiment 1 participants responded by pressing a button either with the mouth or with the hand, in Experiment 2 responses were given with the foot, while a button held either in the mouth or in the hand was used to respond to catch-trials. Abstract words were slower to process in both tasks (concreteness effect). Across the tasks and experiments, emotional concepts had instead a fluctuating pattern, different from those of both concrete and abstract concepts, suggesting that they cannot be considered as a subset of abstract concepts. The interaction between type of concept (abstract, concrete and emotional) and effector (mouth, hand) was not significant in the lexical decision task, likely because it emerged only with tasks implying a deeper processing level. It reached significance, instead, in the recognition tasks. In both experiments abstract concepts were facilitated in the mouth condition compared to the hand condition, supporting our main prediction. Emotional concepts instead had a more variable pattern. Overall, our findings indicate that various kinds of concepts differently activate the mouth and hand effectors, but they also suggest that concepts activate effectors in a flexible and task-dependent way.
Mazzuca et al. (2018) Abstract, emotional and concrete concepts and the activation of mouth-hand effectors. PeerJ 6:e5987 https://doi.org/10.7717/peerj.5987
Comparative cranial morphology of the Late Cretaceous protostegid sea turtle Desmatochelys lowii
Background The phylogenetic placement of Cretaceous marine turtles, especially Protostegidae, is still under debate among paleontologists. Whereas protostegids were traditionally thought to be situated within the clade of recent marine turtles (Chelonioidea), some recent morphological and molecular studies suggest placement along the stem of Cryptodira. The main reason why the evolution of marine turtles is still poorly understood, is in part due to a lack of insights into the cranial anatomy of protostegids. However, a general availability of high-quality fossil material, combined with modern analysis techniques, such as X-ray microtomography, provide ample opportunity to improve this situation. The scope of this study is to help resolve its phylogenetic relationships by providing a detailed description of the external and internal cranial morphology of the extinct protostegid sea turtle Desmatochelys lowii Williston, 1894. Material and Methods This study is based on the well-preserved holotype of Desmatochelys lowii from the Late Cretaceous (middle Cenomanian to early Turonian) Greenhorn Limestone of Jefferson County, Nebraska. The skulls of two recent marine turtles, Eretmochelys imbricata (Linnaeus, 1766) (Cheloniidae) and Dermochelys coriacea Lydekker, 1889 (Dermochelyidae), as well as the snapping turtle Chelydra serpentina (Linnaeus, 1758) (Chelydridae) provide a comparative basis. All skulls were scanned using regular or micro CT scanners and the scans were then processed with the software program Amira to create 3D isosurface models. In total, 81 bones are virtually isolated, figured, and described, including the nature of their contacts. The novel bone contact data is compiled and utilized in a preliminary phenetic study. In addition, an update phylogenetic analysis is conduced that utilizes newly obtained anatomical insights. Results The detailed examination of the morphology of the herein used specimens allowed to explore some features of the skull, to refine the scoring of Desmatochelys lowii in the recent global matrix of turtles, and develop five new characters. The alleged pineal foramen in the type skull of Desmatochelys lowii is shown to be the result of damage. Instead, it appears that the pineal gland only approached the skull surface, as it is in Dermochelys coriacea. Whereas the parasphenoid in confirmed to be absent in hard-shelled sea turtles, ist possible presence in Desmatochelys lowii is unclear. The results of the phenetic study show that Desmatochelys lowii is least similar to the other examined taxa in regards to the nature of its bone contacts, and therefore suggests a placement outside Americhelydia for this protostegid sea turtle. The phylogenetic study results in a placement of Protostegidae along the stem of Chelonioidea, which is a novel position for the group.
Raselli (2018) Comparative cranial morphology of the Late Cretaceous protostegid sea turtle Desmatochelys lowii. PeerJ 6:e5964 https://doi.org/10.7717/peerj.5964
Achieving the impossible: a review of magic-based interventions and their effects on wellbeing
Research has demonstrated that involvement with mainstream performing arts, such as music and dance, can boost wellbeing. This article extends this work by reviewing little-known research on whether learning magic tricks can have an equally beneficial effect. We first present an historic overview of several magic-based interventions created by magicians, psychologists and occupational therapists. We then identify the potential benefits of such interventions, and review studies that have attempted to systematically assess these interventions. The studies have mostly revealed beneficial outcomes, but much of the work is of poor methodological quality (involving small numbers of participants and no control group), and has tended to focus on clinical populations. Finally, we present guidelines for future research in the area, emphasizing the need for more systematic and better-controlled studies.
Wiseman et al. (2018) Achieving the impossible: a review of magic-based interventions and their effects on wellbeing. PeerJ 6:e6081 https://doi.org/10.7717/peerj.6081
Bacterial communities in the digester bed and liquid effluent of a microflush composting toilet system
Lack of access to clean water and sanitation is a major factor impacting public health in communities worldwide. To address this, the S-Lab at Providence College and the Global Sustainable Aid Project developed a microflush composting toilet system to isolate and treat human waste. Solid waste is composted within a filter-digester bed via an aerobic process involving microbes and invertebrates. Liquid waste may be sanitized by solar disinfection (SODIS) or slow sand filtration (SSF). Here, we used 16S rRNA amplicon sequencing of samples from a scaled-down test version of the system to better understand the bacterial component of the toilet system. Immediately after fecal matter was deposited in the test system, the bacterial community of the filter-digester bed at the site of deposition resembled that of the human gut at both the phylum and genus level, which was expected. Genus-level analysis of filter-digester bed samples collected over the next 30 days from the site of deposition showed reduced or undetectable levels of fecal-associated taxa, with the exception of Clostridium XI, which persisted at low abundance throughout the sampling period. Starting with the sample collected on day 4, the bacterial community of the filter-digester bed at the site of deposition was dominated by bacterial taxa commonly associated with environmental sources, reflecting a major shift in bacterial community composition. These data support the toilet system’s capacity for processing solid human waste. We also analyzed how SODIS and SSF sanitization methods affected the bacterial community composition of liquid effluent collected on day 15 from the test system. Untreated and treated liquid effluent samples were dominated by Proteobacteria. At the genus level, the bacterial community of the untreated effluent included taxa commonly associated with environmental sources. In the SODIS-treated effluent, these genera increased in abundance, whereas in the SSF-treated effluent, they were greatly reduced or undetectable. By analyzing operational taxonomic units that were unclassified at the genus level, we observed that SSF appears to introduce new taxa into the treated effluent, likely from the biological film of microbes and small animals that constitutes the key element of SSF. These data will inform continued development of liquid waste handling strategies for the toilet system. Using the test system as an indicator of the performance of the full-scale version, we have shown the effectiveness of the microflush composting toilet system for containing and eliminating gut-associated bacteria, thereby improving sanitation and contributing to better public health in rural and peri-urban communities.
Environmental Contamination and Remediation
Williams et al. (2018) Bacterial communities in the digester bed and liquid effluent of a microflush composting toilet system. PeerJ 6:e6077 https://doi.org/10.7717/peerj.6077
Modelling of the SDF-1/CXCR4 regulated in vivo homing of therapeutic mesenchymal stem/stromal cells in mice
Background Mesenchymal stem/stromal cells (MSCs) are a promising tool for cell-based therapies in the treatment of tissue injury. The stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor 4 (CXCR4) axis plays a significant role in directing MSC homing to sites of injury. However in vivo MSC distribution following intravenous transplantation remains poorly understood, potentially hampering the precise prediction and evaluation of therapeutic efficacy. Methods A murine model of partial ischemia/reperfusion (I/R) is used to induce liver injury, increase the hepatic levels of SDF-1, and study in vivo MSC distribution. Hypoxia-preconditioning increases the expression of CXCR4 in human bone marrow-derived MSCs. Quantitative assays for human DNA using droplet digital PCR (ddPCR) allow us to examine the in vivo kinetics of intravenously infused human MSCs in mouse blood and liver. A mathematical model-based system is developed to characterize in vivo homing of human MSCs in mouse models with SDF-1 levels in liver and CXCR4 expression on the transfused MSCs. The model is calibrated to experimental data to provide novel estimates of relevant parameter values. Results Images of immunohistochemistry for SDF-1 in the mouse liver with I/R injury show a significantly higher SDF-1 level in the I/R injured liver than that in the control. Correspondingly, the ddPCR results illustrate a higher MSC concentration in the I/R injured liver than the normal liver. CXCR4 is overexpressed in hypoxia-preconditioned MSCs. An increased number of hypoxia-preconditioned MSCs in the I/R injured liver is observed from the ddPCR results. The model simulations align with the experimental data of control and hypoxia-preconditioned human MSC distribution in normal and injured mouse livers, and accurately predict the experimental outcomes with different MSC doses. Discussion The modelling results suggest that SDF-1 in organs is an effective in vivo attractant for MSCs through the SDF-1/CXCR4 axis and reveal the significance of the SDF-1/CXCR4 chemotaxis on in vivo homing of MSCs. This in vivo modelling approach allows qualitative characterization and prediction of the MSC homing to normal and injured organs on the basis of clinically accessible variables, such as the MSC dose and SDF-1 concentration in blood. This model could also be adapted to abnormal conditions and/or other types of circulating cells to predict in vivo homing patterns.
Jin et al. (2018) Modelling of the SDF-1/CXCR4 regulated in vivo homing of therapeutic mesenchymal stem/stromal cells in mice. PeerJ 6:e6072 https://doi.org/10.7717/peerj.6072
Conservation implications of primate trade in China over 18 years based on web news reports of confiscations
Primate species have been increasingly threatened by legal and illegal trade in China, mainly for biomedical research or as pets and traditional medicine, yet most reports on trade from China regard international trade. To assess a proxy for amount of national primate trades, we quantified the number of reports of native primate species featuring in unique web news reports from 2000 to 2017, including accuracy of their identification, location where they were confiscated or rescued, and their condition upon rescue. To measure temporal trends across these categories, the time span was divided into three sections: 2000–2005, 2006–2011 and 2012–2017. A total of 735 individuals of 14 species were reported in 372 news reports, mostly rhesus macaques (n = 165, 22.5%, Macaca mulatta) and two species of slow lorises (n = 487, 66.3%, Nycticebus spp.). During the same period, live individuals of rhesus macaques were recorded 206 times (70,949 individuals) in the Convention on International Trade in Endangered Species of Wild Fauna and Flora Trade Database, whereas slow lorises were only recorded four times (nine individuals), indicating that the species originated illegally from China or were illegally imported into China. Due to their rescued locations in residential areas (n = 211, 56.7%), most primates appeared to be housed privately as pets. A higher proportion of ‘market’ rescues during 2006–2011 (χ2 = 8.485, df = 2, p = 0.014), could be partly attributed to an intensive management on wildlife markets since the outbreak of severe acute respiratory syndrome (SARS) in 2003. More than half (68.3%, 502 individuals) of the primate individuals were unhealthy, injured or dead when rescued. Thus, identification and welfare training and capacity-building should be provided to husbandry and veterinary professionals, as well as education to the public through awareness initiatives. The increase in presence of some species, especially slow lorises, with a declining population in restricted areas, also suggests the urgent need for public awareness about the illegal nature of keeping these taxa as pets.
Ni et al. (2018) Conservation implications of primate trade in China over 18 years based on web news reports of confiscations. PeerJ 6:e6069 https://doi.org/10.7717/peerj.6069
Association of urinary activity of MMP-9 with renal impairment in Mexican patients with type 2 diabetes mellitus
Background Diabetic kidney disease is the most common cause of chronic kidney disease (CKD). An early event in diabetic kidney disease is alteration of the glomerular basement membrane and the mesangial expansion. Matrix metalloproteinases (MMP) are a family of endopeptidases responsible for controlling the pathophysiological remodeling of tissues, including renal tissues. MMP-9 in human urine has been proposed as a marker of diabetic nephropathy and urinary tract infections (UTI). Methods A cross-sectional study was conducted in type 2 diabetes mellitus (T2DM) patients who receive first level medical attention in Mexico. We used ELISA to measure MMP-9 levels in the urine of subjects with T2DM ≥ 18 years of age, who fulfilled the clinical requirements for calculation of glomerular filtration rate (GFR), according to the K/DOQI guide, in an attempt to identify whether MMP-9 levels in T2DM differ in patients with and without renal impairment. Univariate and multivariable analyses were performed in order to identify the association between MMP-9 and renal impairment. Results Included in the study were 34 (45%) subjects with renal impairment and 42 (55%) without. In the group with renal impairment, 10 subjects corresponded to stages 1–2 and 24 subjects corresponded to stage 3, according to their values of GFR and urinary albumin, following that proposed by the K/DOQI. No differences were found relating to sex, age, having or not having a partner, education, being able to read and write a message and duration of T2DM. Moreover, no differences were found between the groups in terms of weight, height, body mass index, waist size in general and frequency of UTI. In contrast, serum creatinine and urinary albumin were higher in the group with renal impairment, while GFR was greater in the group without renal impairment. Levels of MMP-9 were greater in women compared to men. Through univariate analysis in the general population, the presence of MMP-9 and that of its percentile 90 (P90) P90 were associated with the renal impairment group; however, in patients without UTI, only the presence of MMP-9 was associated with the renal impairment group, and no association was found with its P90. Multivariate analysis revealed an association between MMP-9 and its P90 with renal impairment. Discussion It is necessary to validate sensitive and non-invasive biological markers of CKD. We demonstrate that the presence and P90 of urinary MMP-9 are associated with renal impairment in Mexican patients with T2DM. While high levels of MMP-9 were associated to females and UTI, the presence of UTI was not associated with the incidence of renal impairment.
García-Tejeda et al. (2018) Association of urinary activity of MMP-9 with renal impairment in Mexican patients with type 2 diabetes mellitus. PeerJ 6:e6067 https://doi.org/10.7717/peerj.6067