32 research outputs found

    Navigating the Mind's Eye: Understanding Gaze Shifts in Visuospatial Bootstrapping

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    Data and materials supporting this work can be found at https://osf.io/sbijz/. Thanks are due to Lotje van der Linden for assistance creating our OpenSesame program, and to support from the National Cyber Security Centre to C.C.M. while this project was being conducted. We also gratefully acknowledge research assistance on pilot work we carried out from Dr. Jaroslaw R. Lelonkiewicz, Viktorija Pratuseviciute, and Lee Robson. Correspondence may be addressed to Candice C. Morey ([email protected]) or Teodor Y. Nikolov ([email protected]).Stephen Darling - ORCID: 0000-0001-7462-6311 https://orcid.org/0000-0001-7462-6311Visuo-spatial bootstrapping refers to the well-replicated phenomena in which serial recall in a purely verbal task is boosted by presenting digits within the familiar spatial layout of a typical telephone keypad. The visuo-spatial bootstrapping phenomena indicates that additional support comes from long-term knowledge of a fixed spatial pattern, and prior experimentation supports the idea that access to this benefit depends on the availability of the visuo-spatial motor system (e.g., Allen et al., 2015). We investigate this by tracking participants’ eye movements during encoding and retention of verbal lists to learn whether gaze patterns support verbal memory differently when verbal information is presented in the familiar visual layout. Participants’ gaze was recorded during attempts to recall lists of seven digits in three formats: centre of the screen, typical telephone keypad, or a spatially identical layout with randomized number placement. Performance was better with the typical than with the novel layout. Our data show that eye movements differ when encoding and retaining verbal information that has a familiar layout compared with the same verbal information presented in a novel layout, suggesting recruitment of different spatial rehearsal strategies. However, no clear link between gaze pattern and recall accuracy was observed, which suggests that gazes play a limited role in retention, at best.inpressinpres

    Navigating the mind's eye: understanding gaze shifts in visuospatial bootstrapping

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    Visuo-spatial bootstrapping refers to the well-replicated phenomena in which serial recall in a purely verbal task is boosted by presenting digits within the familiar spatial layout of a typical telephone keypad. The visuo-spatial bootstrapping phenomena indicates that additional support comes from long-term knowledge of a fixed spatial pattern, and prior experimentation supports the idea that access to this benefit depends on the availability of the visuo-spatial motor system (e.g., Allen et al., 2015). We investigate this by tracking participants’ eye movements during encoding and retention of verbal lists to learn whether gaze patterns support verbal memory differently when verbal information is presented in the familiar visual layout. Participants’ gaze was recorded during attempts to recall lists of seven digits in three formats: centre of the screen, typical telephone keypad, or a spatially identical layout with randomized number placement. Performance was better with the typical than with the novel layout. Our data show that eye movements differ when encoding and retaining verbal information that has a familiar layout compared with the same verbal information presented in a novel layout, suggesting recruitment of different spatial rehearsal strategies. However, no clear link between gaze pattern and recall accuracy was observed, which suggests that gazes play a limited role in retention, at best

    Genetic insights into resting heart rate and its role in cardiovascular disease

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    Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development.</p

    Comparative assessment of An. gambiae and An. stephensi mosquitoes to determine transmission-reducing activity of antibodies against P. falciparum sexual stage antigens.

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    BACKGROUND: With the increasing interest in vaccines to interrupt malaria transmission, there is a demand for harmonization of current methods to assess Plasmodium transmission in laboratory settings. Potential vaccine candidates are currently tested in the standard membrane feeding assay (SMFA) that commonly relies on Anopheles stephensi mosquitoes. Other mosquito species including Anopheles gambiae are the dominant malaria vectors for Plasmodium falciparum in sub-Saharan Africa. METHODS: Using human serum and monoclonal pre-fertilization (anti-Pfs48/45) and post-fertilization (anti-Pfs25) antibodies known to effectively inhibit sporogony, we directly compared SMFA based estimates of transmission-reducing activity (TRA) for An. stephensi and An. gambiae mosquitoes. RESULTS: In the absence of transmission-reducing antibodies, average numbers of oocysts were similar between An. gambiae and An. stephensi. Antibody-mediated TRA was strongly correlated between both mosquito species, and absolute TRA estimates for pre-fertilisation monoclonal antibodies (mAb) showed no significant difference between the two species. TRA estimates for IgG of naturally exposed individuals and partially effective concentrations of anti-Pfs25 mAb were higher for An. stephensi than for An. gambiae. CONCLUSION: Our findings support the use of An. stephensi in the SMFA for target prioritization. As a vaccine moves through product development, better estimates of TRA and transmission-blocking activity (TBA) may need to be obtained in epidemiologically relevant parasite-species combination

    Gene Disruption of Plasmodium falciparum p52 Results in Attenuation of Malaria Liver Stage Development in Cultured Primary Human Hepatocytes

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    Difficulties with inducing sterile and long lasting protective immunity against malaria with subunit vaccines has renewed interest in vaccinations with attenuated Plasmodium parasites. Immunizations with sporozoites that are attenuated by radiation (RAS) can induce strong protective immunity both in humans and rodent models of malaria. Recently, in rodent parasites it has been shown that through the deletion of a single gene, sporozoites can also become attenuated in liver stage development and, importantly, immunization with these sporozoites results in immune responses identical to RAS. The promise of vaccination using these genetically attenuated sporozoites (GAS) depends on translating the results in rodent malaria models to human malaria. In this study, we perform the first essential step in this transition by disrupting, p52, in P. falciparum an ortholog of the rodent parasite gene, p36p, which we had previously shown can confer long lasting protective immunity in mice. These P. falciparum P52 deficient sporozoites demonstrate gliding motility, cell traversal and an invasion rate into primary human hepatocytes in vitro that is comparable to wild type sporozoites. However, inside the host hepatocyte development is arrested very soon after invasion. This study reveals, for the first time, that disrupting the equivalent gene in both P. falciparum and rodent malaria Plasmodium species generates parasites that become similarly arrested during liver stage development and these results pave the way for further development of GAS for human use

    Genetic insights into resting heart rate and its role in cardiovascular disease.

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    Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development

    Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction

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    The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N = 293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease. </p

    Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction

    Get PDF
    The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N = 293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease

    Genetic insights into resting heart rate and its role in cardiovascular disease

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    Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development

    Fungal Planet description sheets: 1182-1283

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    Novel species of fungi described in this study include those from various countries as follows: Algeria, Phaeoacremonium adelophialidum from Vitis vinifera. Antarctica, Comoclathris antarctica from soil. Australia, Coniochaeta salicifolia as endophyte from healthy leaves of Geijera salicifolia, Eremothecium peggii in fruit of Citrus australis, Microdochium ratticaudae from stem of Sporobolus natalensis, Neocelosporium corymbiae on stems of Corymbia variegata, Phytophthora kelmanii from rhizosphere soil of Ptilotus pyramidatus, Pseudosydowia backhousiae on living leaves of Backhousia citriodora, Pseudosydowia indoor oopillyensis, Pseudosydowia louisecottisiae and Pseudosydowia queenslandica on living leaves of Eucalyptus sp. Brazil, Absidia montepascoalis from soil. Chile, Ilyonectria zarorii from soil under Maytenus boaria. Costa Rica, Colletotrichum filicis from an unidentified fern. Croatia, Mollisia endogranulata on deteriorated hardwood. Czech Republic, Arcopilus navicularis from tea bag with fruit tea, Neosetophoma buxi as endophyte from Buxus sempervirens, Xerochrysium bohemicum on surface of biscuits with chocolate glaze and filled with jam. France, Entoloma cyaneobasale on basic to calcareous soil, Fusarium aconidiale from Triticum aestivum, Fusarium juglandicola from buds of Juglans regia. Germany, Tetraploa endophytica as endophyte from Microthlaspi perfoliatum roots. India, Castanediella ambae on leaves of Mangifera indica, Lactifluus kanadii on soil under Castanopsis sp., Penicillium uttarakhandense from soil. Italy, Penicillium ferraniaense from compost. Namibia, Bezerromyces gobabebensis on leaves of unidentified succulent, Cladosporium stipagrostidicola on leaves of Stipagrostis sp., Cymostachys euphorbiae on leaves of Euphorbia sp., Deniquelata hypolithi from hypolith under a rock, Hysterobrevium walvisbayicola on leaves of unidentified tree, Knufia hypolithi and Knufia walvisbayicola from hypolith under a rock, Lapidomyces stipagrostidicola on leaves of Stipagrostis sp., Nothophaeotheca mirabibensis (incl. Nothophaeotheca gen. nov.) on persistent inflorescence remains of Blepharis obmitrata, Paramyrothecium salvadorae on twigs of Salvadora persica, Preussia procaviicola on dung of Procavia sp., Sordaria equicola on zebra dung, Volutella salvadorae on stems of Salvadora persica. Netherlands, Entoloma ammophilum on sandy soil, Entoloma pseudocruentatum on nutrient poor(acid)soil, Entoloma pudens on plant debris, amongst grasses. [...]Leslie W.S. de Freitas and colleagues express their gratitude to Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) for scholarships provided to Leslie Freitas and for the research grant provided to André Luiz Santiago; their contribution was financed by the projects ‘Diversity of Mucoromycotina in the different ecosystems of the Atlantic Rainforest of Pernambuco’ (FACEPE–First Projects Program PPP/ FACEPE/CNPq–APQ–0842-2.12/14) and ‘Biology of conservation of fungi s.l. in areas of Atlantic Forest of Northeast Brazil’ (CNPq/ICMBio 421241/ 2017-9) H.B. Lee was supported by the Graduate Program for the Undiscovered Taxa of Korea (NIBR202130202). The study of O.V. Morozova, E.F. Malysheva, V.F. Malysheva, I.V. Zmitrovich, and L.B. Kalinina was carried out within the framework of a research project of the Komarov Botanical Institute RAS (АААА-А19-119020890079-6) using equipment of its Core Facility Centre ‘Cell and Molecular Technologies in Plant Science’. The work of O. V. Morozova, L.B. Kalinina, T. Yu. Svetasheva, and E.A. Zvyagina was financially supported by Russian Foundation for Basic Research project no. 20-04-00349. E.A. Zvyagina and T.Yu. Svetasheva are grateful to A.V. Alexandrova, A.E. Kovalenko, A.S. Baykalova for the loan of specimens, T.Y. James, E.F. Malysheva and V.F. Malysheva for sequencing. J.D. Reyes acknowledges B. Dima for comparing the holotype sequence of Cortinarius bonachei with the sequences in his database. A. Mateos and J.D. Reyes acknowledge L. Quijada for reviewing the phylogeny and S. de la Peña- Lastra and P. Alvarado for their support and help. Vladimir I. Kapitonov and colleagues are grateful to Brigitta Kiss for help with their molecular studies. This study was conducted under research projects of the Tobolsk Complex Scientific Station of the Ural Branch of the Russian Academy of Sciences (N АААА-А19-119011190112-5). E. Larsson acknowledges the Swedish Taxonomy Initiative, SLU Artdatabanken, Uppsala (dha.2019.4.3-13). The study of D.B. Raudabaugh and colleagues was supported by the Schmidt Science Fellows, in partnership with the Rhodes Trust. Gregorio Delgado is grateful to Michael Manning and Kamash Pillai (Eurofins EMLab P&K) for provision of laboratory facilities. Jose G. Maciá-Vicente acknowledges support from the German Research Foundation under grant MA7171/1-1, and from the Landes-Offensive zur Entwicklung Wissenschaftlich-ökonomischer Exzellenz (LOEWE) of the state of Hesse within the framework of the Cluster for Integrative Fungal Research (IPF). Thanks are also due to the authorities of the Cabañeros National Park and Los Alcornocales Natural Park for granting the collection permit and for support during field work. The study of Alina V. Alexandrova was carried out as part of the Scientific Project of the State Order of the Government of Russian Federation to Lomonosov Moscow State University No. 121032300081-7. Michał Gorczak was financially supported by the Ministry of Science and Higher Education through the Faculty of Biology, University of Warsaw intramural grant DSM 0117600- 13. M. Gorczak acknowledges M. Klemens for sharing a photo of the Białowieża Forest logging site and M. Senderowicz for help with preparing the illustration. Ivona Kautmanová and D. Szabóová were funded by the Operational Program of Research and Development and co-financed with the European Fund for Regional Development (EFRD). ITMS 26230120004: ‘Building of research and development infrastructure for investigation of genetic biodiversity of organisms and joining IBOL initiative’. Ishika Bera, Aniket Ghosh, Jorinde Nuytinck and Annemieke Verbeken are grateful to the Director, Botanical Survey of India (Kolkata), Head of the Department of Botany & Microbiology & USIC Dept. HNB Garhwal University, Srinagar, Garhwal for providing research facilities. Ishika Bera and Aniket Ghosh acknowledge the staff of the forest department of Arunachal Pradesh for facilitating the macrofungal surveys to the restricted areas. Sergey Volobuev was supported by the Russian Science Foundation (RSF project N 19-77- 00085). Aleksey V. Kachalkin and colleagues were supported by the Russian Science Foundation (grant No. 19-74-10002). The study of Anna M. Glushakova was carried out as part of the Scientific Project of the State Order of the Government of Russian Federation to Lomonosov Moscow State University No. 121040800174-6. Tracey V. Steinrucken and colleagues were supported by AgriFutures Australia (Rural Industries Research and Development Corporation), through funding from the Australian Government Department of Agriculture, Water and the Environment, as part of its Rural Research and Development for Profit program (PRJ-010527). Neven Matočec and colleagues thank the Croatian Science Foundation for their financial support under the project grant HRZZ-IP-2018-01-1736 (ForFungiDNA). Ana Pošta thanks the Croatian Science Foundation for their support under the grant HRZZ-2018-09-7081. The research of Milan Spetik and co-authors was supported by Internal Grant of Mendel University in Brno No. IGAZF/ 2021-SI1003. K.C. Rajeshkumar thanks SERB, the Department of Science and Technology, Government of India for providing financial support under the project CRG/2020/000668 and the Director, Agharkar Research Institute for providing research facilities. Nikhil Ashtekar thanks CSIR-HRDG, INDIA, for financial support under the SRF fellowship (09/670(0090)/2020-EMRI), and acknowledges the support of the DIC Microscopy Facility, established by Dr Karthick Balasubramanian, B&P (Plants) Group, ARI, Pune. The research of Alla Eddine Mahamedi and co-authors was supported by project No. CZ.02.1.01/0.0/0.0/16_017/0002334, Czech Republic. Tereza Tejklová is thanked for providing useful literature. A. Polhorský and colleagues were supported by the Operational Program of Research and Development and co-financed with the European fund for Regional Development (EFRD), ITMS 26230120004: Building of research and development infrastructure for investigation of genetic biodiversity of organisms and joining IBOL initiative. Yu Pei Tan and colleagues thank R. Chen for her technical support. Ernest Lacey thanks the Cooperative Research Centres Projects scheme (CRCPFIVE000119) for its support. Suchada Mongkolsamrit and colleagues were financially supported by the Platform Technology Management Section, National Center for Genetic Engineering and Biotechnology (BIOTEC), Project Grant No. P19-50231. Dilnora Gouliamova and colleagues were supported by a grant from the Bulgarian Science Fund (KP-06-H31/19). The research of Timofey A. Pankratov was supported by the Russian Foundation for Basic Research (grant No. 19-04-00297a). Gabriel Moreno and colleagues wish to express their gratitude to L. Monje and A. Pueblas of the Department of Drawing and Scientific Photography at the University of Alcalá for their help in the digital preparation of the photographs, and to J. Rejos, curator of the AH herbarium, for his assistance with the specimens examined in the present study. Vit Hubka was supported by the Charles University Research Centre program No. 204069. Alena Kubátová was supported by The National Programme on Conservation and Utilization of Microbial Genetic Resources Important for Agriculture (Ministry of Agriculture of the Czech Republic). The Kits van Waveren Foundation (Rijksherbariumfonds Dr E. Kits van Waveren, Leiden, Netherlands) contributed substantially to the costs of sequencing and travelling expenses for M. Noordeloos. The work of B. Dima was supported by the ÚNKP-20-4 New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund, and by the ELTE Thematic Excellence Programme 2020 supported by the National Research, Development and Innovation Office of Hungary (TKP2020-IKA-05). The Norwegian Entoloma studies received funding from the Norwegian Biodiversity Information Centre (NBIC), and the material was partly sequenced through NorBOL. Gunnhild Marthinsen and Katriina Bendiksen (Natural History Museum, University of Oslo, Norway) are acknowledged for performing the main parts of the Entoloma barcoding work. Asunción Morte is grateful to AEI/FEDER, UE (CGL2016-78946-R) and Fundación Séneca - Agencia de Ciencia y Tecnología de la Región de Murcia (20866/PI/18) for financial support. Vladimír Ostrý was supported by the Ministry of Health, Czech Republic - conceptual development of research organization (National Institute of Public Health – NIPH, IN 75010330). Konstanze Bensch (Westerdijk Fungal Biodiversity Institute, Utrecht) is thanked for correcting the spelling of various Latin epithets.Peer reviewe
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