bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural basis of malaria transmission blockade by a monoclonal antibody to gamete fusogen HAP2
Authors: Feng Juan , Dong Xianchi , DeCosta Adam , Su Yang , Angrisano Fiona , Sala Katarzyna A. , Blagborough Andrew M. , Lu Chafen , Springer Timothy A. 
Published: October 2021

AbstractHAP2 is a transmembrane gamete fusogen found in multiple eukaryotic kingdoms and is structurally homologous to viral class II fusogens. Studies in Plasmodium have suggested that HAP2 is an attractive target for vaccines that block transmission of malaria. HAP2 has three extracellular domains, arranged in the order D2, D1, and D3. Here, we report monoclonal antibodies against the D3 fragment of Plasmodium berghei HAP2 and crystal structures of D3 in complex with Fab fragments of two of these antibodies, one of which blocks fertilization of Plasmodium berghei in vitro and transmission of malaria in mosquitos. We also show how this Fab binds the complete HAP2 ectodomain with electron microscopy. The two antibodies cross-react with HAP2 among multiple plasmodial species. Our characterization of the Plasmodium D3 structure, HAP2 ectodomain architecture, and mechanism of inhibition provide insights for the development of a vaccine to block malaria transmission.
Modelling Eurasian lynx populations in Western Europe: What prospects for the next 50 years?
Authors: Sarah Bauduin , Estelle Germain , Fridolin Zimmermann , Sylvia Idelberger , Micha Herdtfelder , Marco Heurich , Stephanie Kramer-Schadt , Christophe Duchamp , Nolwenn Drouet-Hoguet , Alain Morand , Laetitia Blanc , Anaïs Charbonnel , Olivier Gimenez 
Published: October 2021

AbstractPersistence of populations may be uncertain for large carnivore species, especially for those established in human-dominated landscapes. Here, we studied the Eurasian lynx in Western Europe established in the Upper Rhine meta-population (i.e., Jura, Vosges-Palatinian and Black Forest populations) and in the Alpine population. These populations are currently considered as endangered or critically endangered due to high anthropogenic mortality, small population size and low genetic diversity, and isolation. We assessed lynx persistence over a 50-year time horizon by implementing a spatially-explicit individual-based model, while accounting for road mortality and habitat selection. Forecasts showed a steady growth rapidly reaching a more stable phase for the Alpine and Jura populations, and a more heterogeneous positive growth with less precision for the Vosges-Palatinian and Black Forest populations. Exchanges of individuals between populations were limited, the Jura population playing the role of a crossroad. Finally, persistence of lynx in Western Europe seems likely on a large scale over the next 50 years. Indeed, simulations showed high female occupancy as well as average lynx density over the whole core areas of the four studied populations. Nevertheless, these results should be interpreted bearing in mind the model limitations concerning the absence of movement barriers and inbreeding depression.
Heterogeneity of Rift Valley fever virus transmission potential across livestock hosts, quantified through a model-based analysis of host viral load and vector infection
Authors: Cecilia Hélène , Vriens Roosmarie , Kortekaas Jeroen , Schreur Paul J. Wichgers , de Wit Mariken , Métras Raphaëlle , Ezanno Pauline , ten Bosch Quirine A. 
Published: October 2021

AbstractRift Valley fever (RVF) is a viral, vector-borne, zoonotic disease. The relative contributions of livestock species to RVFV transmission has not been previously quantified. To estimate their potential to transmit the virus over the course of their infection, we 1) fitted a within-host model to viral RNA and infectious virus measures, obtained daily from infected lambs, calves, and young goats, 2) estimated the relationship between vertebrate host infectious titers and probability to infect mosquitoes, and 3) estimated the net infectiousness of each host species over the duration of their infectious periods, taking into account different survival outcomes for lambs. Our results indicate that the efficiency of viral replication, along with the lifespan of infectious particles, could be sources of heterogeneity between hosts. For similar infectious titers, we found that infection rates in Aedes spp. vectors were significantly higher than in Culex spp. vectors. Consequently, for Aedes infections, we estimated the net infectiousness of lambs to be 2.93 (median) and 3.65 times higher than that of calves and goats, respectively. Among lambs, individuals which eventually died from the infection were 1.93 times more infectious than lambs recovering. Beyond infectiousness, the relative contributions of host species to transmission depend on local ecological factors, including relative abundances and vector host-feeding preferences. Quantifying these contributions will ultimately help design efficient, targeted, surveillance and vaccination strategies.
Geographic distribution and future expansion ofAedes albopictusin the Democratic Republic of the Congo
Authors: Vulu Fabien , Bobanga Thierry Lengu , Sunahara Toshihiko , Futami Kyoko , Jinping Hu , Minakawa Noboru 
Published: October 2021

AbstractAedes albopictuswith an Asian origin has been reported from central African countries. The establishment of this mosquito species poses a serious threat as the vector of various infectious diseases. Since information aboutAe. albopictusin Democratic Republic of the Congo (DRC) is scarce, we investigated the current distribution of this mosquito species. Based on the factors affecting the distribution, we predicted future distribution. We conduced entomological surveys in Kinshasa and three neighboring cities from May 2017 to September 2019. The survey was extended to seven inland cities. A total of 19 environmental variables were examined using the maximum entropy method to identify areas suitable forAe. albopictusto establish a population. We foundAe. albopictusat 21 of 23 sites in Kinshasa and three neighboring cities. For the first timeAe. albopictuswas also found from three of seven inland cities, while it was not found in four cities located in the eastern and southeastern parts of DRC. A maximum entropy model revealed that the occurrence ofAe. albopictuswas positively associated with maximum temperature of the warmest month, and negatively associated with wider mean diurnal temperature range and enhanced vegetation index. The model predicted that most parts of DRC are suitable for the establishment of the mosquito. The unsuitable areas were the eastern and southeastern highlands, which have low temperatures and long dry seasons. We confirmed thatAe. albopictusis well established in Kinshasa and its neighboring cities. The expansion ofAe. albopictusto the inland is ongoing, and in the future the mosquito may establish in most parts of DRC.
Circadian programming of the ellipsoid body sleep homeostat in Drosophila
Authors: Andreani Tomas , Rosensweig Clark , Sisobhan Shiju , Ogunlana Emmanuel , Kath William , Allada Ravi 
Published: October 2021

SummaryHomeostatic and circadian processes collaborate to appropriately time and consolidate sleep and wake. To understand how these processes are integrated, we scheduled brief sleep deprivation at different times of day in Drosophila and find elevated morning rebound compared to evening. These effects depend on discrete morning and evening clock neurons, independent of their roles in circadian locomotor activity. In the R5 ellipsoid body sleep homeostat, we identified elevated morning expression of activity dependent and presynaptic gene expression as well as the presynaptic protein BRUCHPILOT consistent with regulation by clock circuits. These neurons also display elevated calcium levels in response to sleep loss in the morning, but not the evening consistent with the observed time-dependent sleep rebound. These studies reveal the circuit and molecular mechanisms by which discrete circadian clock neurons program a homeostatic sleep center.
Green notes: The rhythms of cyanobacteria exoelectrogenesis as de-composed by the Hilbert-Huang transform
Authors: Okedi Tonny , Yunus Kamran , Fisher Adrian 
Published: October 2021

1AbstractElectrons from cyanobacteria photosynthetic and respiratory systems are implicated in current generated in biophotovoltaic (BPV) devices. However, the pathway that electrons follow to electrodes remains largely unknown, limiting progress of applied research. Here we use Hilbert-Huang transforms to decomposeSynechococcus elongatussp. PCC7942 BPV current density profiles into physically meaningful oscillatory components, and compute their instantaneous frequencies. We develop hypotheses for the genesis of the oscillationsviarepeat experiments with iron-depleted and 20% CO2enriched biofilms. The oscillations exhibit rhythms that are consistent with the state of the art cyanobacteria circadian model, and putative exoelectrogenic pathways. In particular, we observe oscillations consistent with: rhythmic D1:1 (photosystem II core) expression; circadian-controlled glycogen accumulation; circadian phase shifts under modified intracellular %ATP; and circadian period shortening in the absence of the iron-sulphur protein LdpA. We suggest that the extracted oscillations may be used to reverse-identify proteins and/or metabolites responsible for cyanobacteria exoelectrogenesis.
Sexual identity of enterocytes regulates rapamycin-mediated intestinal homeostasis and lifespan extension
Authors: Regan Jennifer C , Lu Yu-Xuan , Ureña Enric , Meilenbrock Ralf , Catterson James H , Kißler Disna , Partridge Linda 
Published: October 2021

AbstractPharmacological attenuation of mTOR by rapamycin and other compounds presents a promising route for delay of ageing-related pathologies, including intestinal cancers. Here, we show that rapamycin treatment in Drosophila extends lifespan in females but not in males. Female-specific, age-related gut pathology and impaired intestinal barrier function are both markedly slowed by rapamycin treatment, mediated by increased autophagy. Upon rapamycin treatment, female intestinal enterocytes increase autophagy, via the H3/H4 histone-Bchs axis, while male enterocytes show high basal levels of autophagy that do not increase further upon rapamycin treatment. Sexual identity of enterocytes alone, determined by the expression of transformerFemale, dictates sexually dimorphic cell size, H3/H4-Bchs expression, basal rates of autophagy, fecundity, intestinal homeostasis and extension of lifespan in response to rapamycin. This study highlights that tissue sex determines regulation of metabolic processes by mTOR and the efficacy of mTOR-targeted, anti-ageing drug treatments.
Early epigenetic influence on EGR1, KLF2 and KLF4 transcriptional network associates with alteration of HSCs quiescence
Authors: Pelletier Alexandre , Carrier Arnaud , Zhao Yong Mei , Canouil Mickaël , Derhourhi Mehdi , Durand Emmanuelle , Berberian-Ferrato Lionel , Greally John , Hughes Francine , Froguel Philippe , Bonnefond Amélie , Delahaye Fabien 
Published: October 2021

SummaryExcessive fetal growth is associated with DNA methylation alterations in human hematopoietic stem and progenitor cells (HSPC), but their functional impact remains elusive. We implemented an integrative analysis combining single-cell epigenomics, single-cell transcriptomics, and in vitro analyses to functionally link DNA methylation changes to putative alterations of HSPC functions. We showed in hematopoietic stem cells (HSC) from large for gestational age neonates that both DNA hypermethylation and chromatin rearrangement target a specific network of transcription factors known to sustain stem cell quiescence. In parallel, we found a decrease expression of key genes regulating HSC differentiation including EGR1, KLF2, SOCS3, and JUNB. Our functional analyses showed that this epigenetic programming was associated with a decreased ability for HSCs to stay quiescent. Taken together, our multimodal approach using single-cell (epi)genomics showed that human fetal overgrowth affects hematopoietic stem cells quiescence maintenance via epigenetic programming.
Altered collective mitochondrial dynamics in an Arabidopsis msh1 mutant compromising organelle DNA maintenance
Authors: Chustecki Joanna M. , Etherington Ross D. , Gibbs Daniel J. , Johnston Iain G. 
Published: October 2021

SummaryMitochondria form highly dynamic populations in the cells of plants (and all eukaryotes). The characteristics of this collective behaviour, and how it is influenced by nuclear features, remain to be fully elucidated. Here, we use a recently-developed quantitative approach to reveal and analyse the physical and collective “social” dynamics of mitochondria in an Arabidopsis msh1 mutant where organelle DNA maintenance machinery is compromised. We use a newly-created line combining the msh1 mutant with mitochondrially-targeted GFP, and characterise mitochondrial dynamics with a combination of single-cell timelapse microscopy, computational tracking and network analysis. The collective physical behaviour of msh1 mitochondria is altered from wildtype in several ways: mitochondria become less evenly spread, and networks of inter-mitochondrial encounters become more connected with greater potential efficiency for inter-organelle exchange. We find that these changes are similar to those observed in friendly, where mitochondrial dynamics are altered by a physical perturbation, suggesting that this shift to higher connectivity may reflect a general response to mitochondrial challenges.
Tickle contagion in the somatosensory cortex
Authors: Kaufmann Lena V. , Brecht Michael , Ishiyama Shimpei 
Published: October 2021

AbstractThe cellular mechanisms of emotional contagion are unknown. We investigated tickle contagion and the underlying neuronal representations in rats. We recorded trunk somatosensory cortex activity of observer rats while they received tickling, audio-visual playback of tickling footage, and while they witnessed tickling of demonstrator rats. Observers vocalized, and showed “Freudensprünge” (“joy jumps”) during witnessing live tickling, while they showed little behavioral responses to playbacks. A fraction of trunk somatosensory neurons responded to both direct and witnessed tickling in action-specific manner. The correlation between direct and witnessed tickling responses increased towards deeper cortical layers. Tickle-mirror neurons but not non-mirror neurons discharged prior to and during vocalizations and hence might drive contagious ‘laughter’. We conclude that trunk somatosensory cortex represents mirrored ticklishness.
TransferGWAS: GWAS of images using deep transfer learning
Authors: Kirchler Matthias , Konigorski Stefan , Norden Matthias , Meltendorf Christian , Kloft Marius , Schurmann Claudia , Lippert Christoph 
Published: October 2021

AbstractMotivationMedical images can provide rich information about diseases and their biology. However, investigating their association with genetic variation requires non-standard methods. We propose transferGWAS, a novel approach to perform genome-wide association studies directly on full medical images. First, we learn semantically meaningful representations of the images based on a transfer learning task, during which a deep neural network is trained on independent but similar data. Then, we perform genetic association tests with these representations.ResultsWe validate the type I error rates and power of transferGWAS in simulation studies of synthetic images. Then we apply transferGWAS in a genome-wide association study of retinal fundus images from the UK Biobank. This first-of-a-kind GWAS of full imaging data yielded 60 genomic regions associated with retinal fundus images, of which 7 are novel candidate loci for eye-related traits and diseases.Contactmatthias.kirchler@hpi.de, christoph.lippert@hpi.deSupplementary informationOur method is implemented in Python and available at https://github.com/mkirchler/transferGWAS/
Longitudinal single-cell transcriptional dynamics throughout neurodegeneration in SCA1
Authors: Tejwani Leon , Ravindra Neal G , Nguyen Billy , Luttik Kimberly , Lee Changwoo , Gionco John , Kim Kristen , Yoon Jennifer , Haidery Fatema , Ro Hannah , Ni Luhan , Orr Harry T , Ranum Laura PW , Shakkottai Vikram G , Faust Phyllis L , van Dijk David , Lim Janghoo 
Published: October 2021

SUMMARYNeurodegeneration is a protracted process involving progressive changes in myriad cell types that ultimately result in neuronal death. Changes in vulnerable neuronal populations are highly influenced by concomitant changes in surrounding cells, complicating experimental approaches to interrogate the simultaneous events that underlie neurodegeneration. To dissect how individual cell types within a heterogeneous tissue contribute to the pathogenesis and progression of a neurodegenerative disorder, we performed longitudinal single-nucleus RNA sequencing of the mouse and human spinocerebellar ataxia type 1 (SCA1) cerebellum, establishing continuous dynamic trajectories of each population. Furthermore, we defined the precise transcriptional changes that precede loss of Purkinje cells and identified early oligodendroglial impairments that can profoundly impact cerebellar function. Finally, we applied a deep learning method to accurately predict disease state and identify drivers of disease. Together, this work uncovers new roles for diverse cerebellar cell types in SCA1 and provides a generalizable analysis framework for studying neurodegeneration.
Hierarchical Bayesian Modeling of the Relationship between Task Related Hemodynamic Responses and Cortical Excitability
Authors: Cai Zhengchen , Pellegrino Giovanni , Lina Jean-Marc , Benali Habib , Grova Christophe 
Published: October 2021

AbstractBackgroundInvestigating the relationship between task-related hemodynamic responses and cortical excitability is challenging because it requires simultaneous measurement of hemodynamic responses while applying non-invasive brain stimulation. Moreover, cortical excitability and task-related hemodynamic responses are both associated with inter-/intra-subject variability. To reliably assess such a relationship, we applied hierarchical Bayesian modeling.MethodsThis study involved 16 healthy subjects who underwent simultaneous Paired Associative Stimulation (PAS10, PAS25, Sham) while monitoring brain activity using functional Near-Infrared Spectroscopy (fNIRS), targeting the primary motor cortex (M1). Cortical excitability was measured by Motor Evoked Potentials (MEPs), and the motor task-related hemodynamic responses were measured using fNIRS 3D reconstructions. We constructed three models to investigate: 1) PAS effects on the M1 excitability; 2) PAS effects on fNIRS hemodynamic responses to a finger tapping task, and 3) the correlation between PAS effects on M1 excitability and PAS effects on task-related hemodynamic responses.ResultsSignificant increase in cortical excitability was found following PAS25, whereas a small reduction of the cortical excitability was shown after PAS10 and a subtle increase occurred after sham. Both HbO and HbR absolute amplitudes increased after PAS25 and decreased after PAS10. The probability of the positive correlation between modulation of cortical excitability and hemodynamic activity was 0.77 for HbO and 0.79 for HbR.ConclusionWe demonstrated that PAS stimulation modulates task-related cortical hemodynamic responses in addition to M1 excitability. Moreover, the positive correlation between PAS modulations of excitability and hemodynamics brought insight into understanding the fundamental properties of cortical function and cortical excitability.
Dynamic Cell Imaging: application to the diatom Phaeodactylum tricornutum under environmental stresses
Authors: Bey Houda , Charton Florent , de Carvalho Helena Cruz , Liu Shun , Dorrell Richard G. , Bowler Chris , Boccara Claude , Boccara Martine 
Published: October 2021

ABSTRACTThe dynamic movement of cell organelles is an important and poorly understood component of cellular organisation and metabolism. In this work we present a non-invasive non-destructive method (Dynamic Cell Imaging, DCI) based on light scattering and interferometry to monitor dynamic events within photosynthetic cells using the diatom Phaeodactylum tricornutum as a model system. For this monitoring we acquire few seconds movies of the signals that are related to the motion of dynamic structures within the cell (denoted scatterers), followed by a statistical analysis of each pixel time series. Illuminating P.tricornutum with LEDs of different wavelengths associated to short pulsed or continuous-wave modes of illumination revealed that dynamic movements depend on chloroplast activity, in agreement with the reduction in the number of pixels with dynamic behaviour after addition of photosystemII inhibitors. We studied P. tricornutum under two environmentally relevant stresses, iron and phosphate deficiency. The major dynamic sites were located within lipid droplets and chloroplast envelope membranes. By comparing standard deviation and cumulative sum analysis of the time series, we showed that within the droplets two types of scatterer movement could be observed: random motions (Brownian type) but also anomalous movements corresponding to a drift which may relate to molecular fluxes within a cell. The method appears valuable for studying the effects of various environments on a large variety of microalgae in the laboratory as well as in natural aquatic environments.HIGHLIGHTsLight scattering an alternative to fluorescence to rapidly evidence dynamic processes.Lipid droplets the major metabolic active sites under stressA non-destructive visualisation method for laboratory microalgae and aquatic samples..SIGNIFICANCE STATEMENTLight scattering could be an alternative to fluorescence techniques to study dynamic processes within photosynthetic cells. We used a method combining light scattering and interferometry to analyse movements of intracellular scatterers in the marine diatom Phaedactylum tricornutum under two environmentally relevant stresses, iron and phosphate deficiency. Lipid droplets were the major active sites under stress. The method which is rapid and non destructive can be broadly expanded to study other microalgae and their stress responses, in the laboratory and in aquatic environments.
Inference of cell state transitions and cell fate plasticity from single-cell with MARGARET
Authors: Pandey Kushagra , Zafar Hamim 
Published: October 2021

AbstractDespite recent advances in inferring cellular dynamics using single-cell RNA-seq data, existing trajectory inference (TI) methods face difficulty in accurately reconstructing cell-state manifold and inferring trajectory and cell fate plasticity for complex topologies. We present MARGARET, a novel TI method that utilizes a deep unsupervised metric learning-based approach for inferring the cellular embeddings and employs a novel measure of connectivity between cell clusters and a graph-partitioning approach to reconstruct complex trajectory topologies. MARGARET utilizes the inferred trajectory for determining terminal states and inferring cell-fate plasticity using a scalable absorbing Markov Chain model. On a diverse simulated benchmark, MARGARET out-performed state-of-the-art methods in recovering global topology and cell pseudotime ordering. When applied to experimental datasets from hematopoiesis, embryogenesis, and colon differentiation, MARGARET reconstructed major lineages and associated gene expression trends, better characterized key branching events and transitional cell types, and identified novel cell types, and branching events that were previously uncharacterized.