bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatial alignment between faces and voices improves selective attention to audio-visual speech
Authors: Fleming Justin T. , Maddox Ross K. , Shinn-Cunningham Barbara G. 
Published: April 2021

AbstractThe ability to see a talker’s face has long been known to improve speech intelligibility in noise. This perceptual benefit depends on approximate temporal alignment between the auditory and visual speech components. However, the practical role that cross-modal spatial alignment plays in integrating audio-visual (AV) speech remains unresolved, particularly when competing talkers are present. In a series of online experiments, we investigated the importance of spatial alignment between corresponding faces and voices using a paradigm that featured both acoustic masking (speech-shaped noise) and attentional demands from a competing talker. Participants selectively attended a Target Talker’s speech, then identified a word spoken by the Target Talker. In Exp. 1, we found improved task performance when the talkers’ faces were visible, but only when corresponding faces and voices were presented in the same hemifield (spatially aligned). In Exp. 2, we tested for possible influences of eye position on this result. In auditory-only conditions, directing gaze toward the distractor voice reduced performance as predicted, but this effect could not fully explain the cost of AV spatial misalignment. Finally, in Exp. 3 and 4, we show that the effect of AV spatial alignment changes with noise level, but this was limited by a floor effect: due to the use of closed-set stimuli, participants were able to perform the task relatively well using lipreading alone. However, comparison between the results of Exp. 1 and Exp. 3 suggests that the cost of AV misalignment is larger at high noise levels. Overall, these results indicate that spatial alignment between corresponding faces and voices is important for AV speech integration in attentionally demanding communication settings.
Ligands binding to the cellular prion protein induce its protective proteolytic release with therapeutic potential in neurodegenerative proteinopathies
Authors: Linsenmeier Luise , Mohammadi Behnam , Shafiq Mohsin , Frontzek Karl , Bär Julia , Shrivastava Amulya N. , Damme Markus , Schwarz Alexander , Da Vela Stefano , Massignan Tania , Jung Sebastian , Correia Angela , Schmitz Matthias , Puig Berta , Hornemann Simone , Zerr Inga , Tatzelt Jörg , Biasini Emiliano , Saftig Paul , Schweizer Michaela , Svergun Dimitri , Amin Ladan , Mazzola Federica , Varani Luca , Thapa Simrika , Gilch Sabine , Schätzl Hermann , Harris David A. , Triller Antoine , Mikhaylova Marina , Aguzzi Adriano , Altmeppen Hermann C. , Glatzel Markus 
Published: April 2021

AbstractThe cellular prion protein (PrPC) is a central player in neurodegenerative diseases caused by protein misfolding, such as prion diseases or Alzheimer’s disease (AD). Expression levels of this GPI-anchored glycoprotein, especially at the neuronal cell surface, critically correlate with various pathomechanistic aspects underlying these diseases, such as templated misfolding (in prion diseases) and neurotoxicity and, hence, with disease progression and severity. In stark contrast to cell-associated PrPC, soluble extracellular forms or fragments of PrP are linked with neuroprotective effects, which is likely due to their ability to interfere with neurotoxic disease-associated protein conformers in the interstitial fluid. Fittingly, the endogenous proteolytic release of PrPCby the metalloprotease ADAM10 (‘shedding’) was characterized as a protective mechanism. Here, using a recently generated cleavage-site specific antibody, we shed new light on earlier studies by demonstrating that shed PrP (sPrP) negatively correlates with conformational conversion (in prion disease) and is markedly redistributed in murine brain in the presence of prion deposits or AD-associated amyloid plaques indicating a blocking and sequestrating activity. Importantly, we reveal that administration of certain PrP-directed antibodies and other ligands results in increased PrP shedding in cells and organotypic brain slice cultures. We also provide mechanistic and structural insight into this shedding-stimulating effect. In addition, we identified a striking exception to this, as one particular neuroprotective antibody, due to its special binding characteristics, did not cause increased shedding but rather strong surface clustering followed by fast endocytosis and degradation of PrPC. Both mechanisms may contribute to the beneficial action described for some PrP-directed antibodies/ligands and pave the way for new therapeutic strategies against devastating and currently incurable neurodegenerative diseases.
Hierarchical Computational Anatomy: Unifying the Molecular to Tissue Continuum Via Measure Representations of the Brain
Authors: Miller Michael , Tward Daniel , Trouvé Alain 
Published: April 2021

AbstractObjectiveThe objective of this research is to unify the molecular representations of spatial transcriptomics and cellular scale histology with the tissue scales of Computational Anatomy for brain mapping.Impact statementWe present a unified representation theory for brain mapping based on geometric measures of the micro-scale phenotypes of molecular disease simultaneously with the connectomic scales of complex interacting brain circuits.IntroductionMapping across coordinate systems in computational anatomy allows us to understand structural and functional properties of the brain at the millimeter scale. New measurement technologies in digital pathology and spatial transcriptomics allow us to measure the brain molecule by molecule and cell by cell based on protein and transcriptomic identity. We currently have no mathematical representations for integrating consistently the tissue limits with the molecular particle descriptions. The formalism derived here demonstrates the methodology for transitioning consistently from the molecular scale of quantized particles – as first introduced by Dirac as the class of generalized functions – to the continuum and fluid mechanics scales appropriate for tissue.MethodsWe introduce two methods based on notions of generalized function geometric measures and statistical mechanics. We use generalized functions expanded to include functional geometric descriptions - electrophysiology, transcriptomic, molecular histology – to represent the molecular biology scale integrated with a Boltzman like procedure to pass from the sparse particles to empirical probability laws on the functional state of the tissue.ResultsWe demonstrate a unified mapping methodology for transferring molecular information in the transcriptome and histological scales to the human atlas scales for understanding Alzheimer’s disease.ConclusionsWe demonstrate a unified brain mapping theory for molecular and tissue scales based on geometric measure representations.
Protective efficacy of an orf virus-vector encoding the hemmagglutinin and the nucleoprotein of influenza A virus in swine
Authors: Joshi Lok R. , Knudsen David , Pineyro Pablo , Dhakal Santhosh , Renukaradhya Gourapura J. , Diel Diego G. 
Published: April 2021

AbstractSwine influenza is a highly contagious respiratory disease of pigs caused by influenza A viruses (IAV-S). IAV-S causes significant economic losses to the swine industry and poses constant challenges to public health due to its zoonotic potential. Thus effective IAV-S vaccines are highly desirable and would benefit both animal and human health. Here, we developed two recombinant orf viruses, expressing the hemagglutinin (HA) gene (OV-HA) or both the HA and the nucleoprotein (NP) genes of IAV-S (OV-HA-NP). The immunogenicity and protective efficacy of these two recombinant viruses were evaluated in pigs. Both OV-HA and OV-HA-NP recombinants elicited robust virus neutralizing antibody response in pigs. Notably, although both recombinant viruses elicited IAV-S-specific T-cell responses, the frequency of IAV-S specific proliferating T cells secreting IFN-γ upon re-stimulation was higher in OV-HA-NP-immunized animals than in the OV-HA group. Importantly, IgG1/IgG2 isotype ELISAs revealed that immunization with OV-HA induced Th2-biased immune responses, whereas immunization with OV-HA-NP virus resulted in a Th1-biased immune response. While pigs immunized with either OV-HA or OV-HA-NP were protected when compared to non-immunized controls, immunization with OV-HA-NP resulted in better protective efficacy as evidenced by reduced virus shedding in nasal secretions and reduced viral load in the lung. This study demonstrates the potential of ORFV-based vector for control of swine influenza virus in swine.ImportanceEffective influenza A virus (IAV-S) vaccines capable of providing robust protection to genetically diverse IAV-S in swine are lacking. Here, we explored the potential of orf virus based vectors expressing the hemagglutining (HA) or both the HA and the nucleoprotein (NP) genes of influena A virus (IAV-S) in eliciting protection against IAV-S in pigs. We observed that both recombinant viruses elicited IAV-S-specific humoral and cell-mediated immune responses in pigs. Addition of the NP and co-expression of this protein with HA, another major influenza protective antigen, resulted in higher T cell responses which presumably led to better protection in OV-HA-NP immunized animals, as evidenced by lower levels of virus shedding and viral load in lungs. This study highlights the the potential of ORFV as a vector platform for vaccine delivery against IAV-S. Results here provide the foundation for future development of broadly protective ORFV-based vectors for IAV-S for use in swine.
Cuticular hydrocarbons are associated with mating success and insecticide resistance in malaria vectors
Authors: Adams Kelsey L. , Sawadogo Simon P. , Nignan Charles , Niang Abdoulaye , Paton Douglas G. , Shaw W. Robert , South Adam , Wang Jennifer , Itoe Maurice A. , Werling Kristine , Dabiré Roch K. , Diabaté Abdoulaye , Catteruccia Flaminia 
Published: April 2021

AbstractAnopheles coluzziifemales, important malaria vectors in Africa, mate only once in their lifetime. Mating occurs in aerial swarms with a high male-to-female ratio, where the traits underlying male mating success are largely unknown. Here, we investigated whether cuticular hydrocarbons (CHCs) influence mating success in natural mating swarms in Burkina Faso. As insecticides are widely used in this area for malaria control, we also determined whether CHCs affect insecticide resistance levels. We find that mated males have higher CHC abundance than unmated controls, suggesting CHCs could be a determinant of mating success. Additionally, mated males have higher insecticide resistance under pyrethroid challenge, and we show a link between resistance intensity and CHC abundance. Taken together, our results reveal overlapping roles played by CHCs in mate choice and insecticide resistance, and point to sexual selection for insecticide resistance traits that limit the efficacy of our best malaria control tools.
Pivotal role of PDE10A in the integration of dopamine signals in mice striatal D1 and D2 medium-sized spiny neurones
Authors: Mota Élia , Bompierre Ségolène , Betolngar Dahdjim , Castro Liliana R.V. , Vincent Pierre 
Published: April 2021

AbstractDopamine in the striatum plays a crucial role in reward processes and action selection. Dopamine signals are transduced by D1and D2dopamine receptors which trigger mirror effects through the cAMP/PKA signalling cascade in D1 and D2 medium-sized spiny neurones (MSNs). Phosphodiesterases (PDEs), which determine the profile of cAMP signals, are highly expressed in MSNs, but their respective roles in dopamine signal integration remain poorly understood. We used genetically-encoded FRET biosensors to monitor at the single cell level the functional contribution of PDE2A, PDE4 and PDE10A in the changes of the cAMP/PKA response to transient and continuous dopamine in mouse striatal brain slices. We found that PDE2A, PDE4 and PDE10A operate on the moderate to high cAMP levels elicited by D1or A2Areceptor stimulation. In contrast, only PDE10A is able to reduce cAMP down to baseline in both type of neurones, leading to the dephosphorylation of PKA substrates. PDE10A is therefore critically required for dopamine signal integration in both D1 and D2 MSNs.
Assessing the origins of the European Plagues following the Black Death: a synthesis of genomic, historical and ecological information
Authors: Bramanti Barbara , Wu Yarong , Yang Ruifu , Cui Yujun , Stenseth Nils Chr. 
Published: April 2021

AbstractThe Second Plague Pandemic started in Europe with the Black Death in 1346 and lasted until the 19thcentury. Based on ancient DNA studies, there is a scientific disagreement over whether the bacterium,Yersinia pestis, came into Europe once (Hypothesis 1), or repeatedly over the following four centuries (Hypothesis 2). Here we synthesize the most updated phylogeny together with historical, archeological, evolutionary and ecological information. On the basis of this holistic view, we conclude that Hypothesis 2 is the most plausible. We also suggest thatY. pestislineages might have developed attenuated virulence during transmission, which can explain the convergent evolutionary signals, includingpla-decay, that appeared at the end of the pandemics.Significance StatementOver the last few years there has been a great deal of scientific debate regarding whether the plague bacterium,Yersinia pestis, spread from a Western European reservoir during the Second Plague Pandemic, or if it repeatedly came to Europe from Asia. Here we make a synthesis of the available evidence, including genomes of ancient DNA, historical, archeological and ecological information. We conclude that the bacterium most likely came to Europe from Asia several times during the Second Plague Pandemic.
Unique metabolic strategies in Hadean analogues reveal hints for primordial physiology
Authors: Nobu Masaru Konishi , Nakai Ryosuke , Tamazawa Satoshi , Mori Hiroshi , Toyoda Atsushi , Ijiri Akira , Suzuki Shino , Kurokawa Ken , Kamagata Yoichi , Tamaki Hideyuki 
Published: April 2021

AbstractPrimordial microorganisms are postulated to have emerged in H2-rich alkaline Hadean serpentinite-hosted environments with homoacetogenesis as a core metabolism. However, investigation of two modern serpentinization-active analogues of early Earth reveals that conventional H2-/CO2-dependent homoacetogenesis is thermodynamically unfavorable in situ due to picomolar CO2 levels. Through metagenomics and thermodynamics, we discover unique taxa capable of metabolism adapted to the habitat. This included a novel deep-branching phylum, “Ca. Lithoacetigenota”, that exclusively inhabits Hadean analogues and harbors genes encoding alternative modes of H2-utilizing lithotrophy. Rather than CO2, these metabolisms utilize reduced carbon compounds detected in situ presumably serpentinization-derived: formate and glycine. The former employs a partial homoacetogenesis pathway and the latter a distinct pathway mediated by a rare selenoprotein – the glycine reductase. A survey of serpentinite-hosted system microbiomes shows that glycine reductases are diverse and nearly ubiquitous in Hadean analogues. “Ca. Lithoacetigenota” glycine reductases represent a basal lineage, suggesting that catabolic glycine reduction is an ancient bacterial innovation for gaining energy from geogenic H2 even under serpentinization-associated hyperalkaline, CO2-poor conditions. This draws remarkable parallels with ancestral archaeal H2-driven methyl-reducing methanogenesis recently proposed. Unique non-CO2-reducing metabolic strategies presented here may provide a new view into metabolisms that supported primordial life and the diversification of LUCA towards Archaea and Bacteria.
Antibody Conversion rates to SARS-CoV-2 in Saliva from Children Attending Summer Schools in Barcelona, Spain
Authors: Dobaño Carlota , Alonso Selena , Fernández de Sevilla Mariona , Vidal Marta , Jiménez Alfons , Tomas Gemma Pons , Jairoce Chenjerai , Melé Casas María , Rubio Rocío , Hernández García María , Ruiz-Olalla Gemma , Girona-Alarcón Mònica , Barrios Diana , Santano Rebeca , Mitchell Robert A. , Puyol Laura , Mayer Leonie , Chi Jordi , Melero Natalia Rodrigo , Carolis Carlo , Garcia-Miquel Aleix , Bonet-Carne Elisenda , Claverol Joana , Cubells Marta , Fortuny Claudia , Fumadó Victoria , Jou Cristina , Muñoz-Almagro Carmen , Izquierdo Luis , Bassat Quique , Gratacós Eduard , Aguilar Ruth , García-García Juan José , Moncunill Gemma , Jordan Iolanda 
Published: April 2021

ABSTRACTSurveillance tools to estimate infection rates in young populations are essential to guide recommendations for school reopening and management during viral epidemics. Ideally, field-deployable non-invasive, sensitive techniques are required to detect low viral load exposures among asymptomatic children. We determined SARS-CoV-2 antibody conversion by high-throughput Luminex assays in saliva samples collected weekly in 1,509 children and 396 adults in 22 Summer schools and 2 pre-schools in 27 venues in Barcelona, Spain, from June 29thto July 31st2020, between the first and second COVID-19 pandemic waves. Saliva antibody conversion defined as ≥4-fold increase in IgM, IgA and/or IgG levels to SARS-CoV-2 antigens between two visits over a 5-week period was 3.22% (49/1518), or 2.36% if accounting for potentially cross-reactive antibodies, six times higher than the cumulative infection rate (0.53%) by weekly saliva RT-PCR screening. IgG conversion was higher in adults (2.94%, 11/374) than children (1.31%, 15/1144) (p=0.035), IgG and IgA levels moderately increased with age, and antibodies were higher in females. Most antibody converters increased both IgG and IgA antibodies but some augmented either IgG or IgA, with a faster decay over time for IgA than IgG. Nucleocapsid rather than spike was the main antigen target. Anti-spike antibodies were significantly higher in individuals not reporting symptoms than symptomatic individuals, suggesting a protective role against COVID-19. To conclude, saliva antibody profiling including three isotypes and multiplexing antigens is a useful and more user-friendly tool for screening pediatric populations to determine SARS-CoV-2 exposure and guide public health policies during pandemics.
Activation of EGFR signaling by Tc-Vein and Tc-Spitz regulates the metamorphic transition in the red flour beetleTribolium castaneum
Authors: Chafino Sílvia , Martín David , Franch-Marro Xavier 
Published: April 2021

ABSTRACTAnimal development relies on a sequence of specific stages that allow the formation of adult structures with a determined size. In general, juvenile stages are dedicated mainly to growth, whereas last stages are devoted predominantly to the maturation of adult structures. In holometabolous insects, metamorphosis marks the end of the growth period as the animals stops feeding and initiate the final differentiation of the tissues. This transition is controlled by the steroid hormone ecdysone produced in the prothoracic gland. In Drosophila different signals have been shown to regulate the production of ecdysone, such as PTTH/Torso, TGFß and Egfr signaling. However, to which extent the role of these signals is conserved remains unknown. Here, we study the role of Egfr signaling in post-embryonic development of the basal holometabolous beetleTribolium castaneum. We show thatTc-Egfr and Tc-pointedare required to induced a proper larval-pupal transition through the control of the expression of ecdysone biosynthetic genes. Furthermore, we identified an additional Tc-Egfr ligand in theTriboliumgenome, the neuregulin-like protein Tc-Vein (Tc-Vn), which contributes to induce larval-pupal transition together with Tc-Spitz (Tc-Spi). Interestingly, we found that in addition to the redundant role in the control of pupa formation, each ligand possesses different functions in organ morphogenesis. Whereas Tc-Spi acts as the main ligand in urogomphi and gin traps, Tc-Vn is required in wings and elytra. Altogether, our findings show that inTribolium, post-embryonic Tc-Egfr signaling activation depends on the presence of two ligands and that its role in metamorphic transition is conserved in holometabolous insects.
BET family members Bdf1/2 modulate global transcription initiation and elongation inSaccharomyces cerevisiae
Authors: Donczew Rafal , Hahn Steven 
Published: April 2021

AbstractHuman bromodomain-containing BET family members are promising targets for therapy of cancer and immunoinflammatory diseases, but their mechanisms of action and functional redundancies are poorly understood. Bdf1/2, yeast homologues of the human BET factors, were previously proposed to target transcription factor TFIID to acetylated histone H4, analogous to bromodomains that are present within the largest subunit of metazoan TFIID. We investigated the genome-wide roles of Bdf1/2 and found that their important contributions to transcription extend beyond TFIID function, as transcription of many genes is more sensitive to Bdf1/2 than to TFIID depletion. Bdf1/2 co-occupy the majority of yeast promoters and affect preinitiation complex formation through recruitment of TFIID, Mediator and basal transcription factors to chromatin. Surprisingly, we discovered that hypersensitivity of genes to Bdf1/2 depletion results from combined defects in transcription initiation and processive elongation, a striking functional similarity to human BET proteins, most notably Brd4. Our results establish Bdf1/2 as critical for yeast transcription and provide important mechanistic insights into the function of BET proteins in all eukaryotes.
A tomato prolyl-4-hydroxylase causes relocation of abscission zone and alters abscission kinetics
Authors: Perrakis Andreas , Denic Dusan , Blazakis Konstantinos N. , Giannoutsou Eleni , Kaloudas Dimitrios , Bita Craita E. , Rizou Myrto , Krokida Afrodite , Kouhen Mohamed , Lazaridou Athina , Mekkaoui Khansa , Belaidi Samia , Zein Zeina El , Khalil Mohab , Ezzat Lamia , Youssef Noureldine , Kosma Maria , González Anna G. , Monzer Aline , Papantoniou Dimitra , Varnava - Tello Antri , Bouzayen Mondher , Adamakis Ioannis-Dimosthenis S. , Driouich Azeddine , Billiaderis Costas G. , Kalogerakis Nicolas , Kalaitzis Panagiotis 
Published: April 2021

AbstractThe detachment of organs is controlled by highly regulated molecular mechanisms. The position of the tomato abscission zone (AZ) is defined by the ratio of the proximal to distal part of the pedicel. In this study, the ratio was altered due to a shift in the position of the AZ which was attributed to shorter and longer pedicels of SlP4H3 RNAi and OEX lines due to changes on cell division and expansion in AZ and distal part. This might be associated with LM2- and JIM8-AGPs which increased in OEX and decreased in RNAi lines throughout the pedicel. The JIM13 AGPs were downregulated in the flower AZ of OEX lines, pointing to a role on abscission regulation. In addition, Co-IP in flower AZ with SlP4H3-GFP fusion proteins showed interaction with LM2-, JIM13- and JIM8-epitopes suggesting proline hydroxylation by SlP4H3. The lower content of methyl-esterified HGs and higher of demethyl-esterified HGs in the AZs of RNAi lines might be responsible for increased rigidity of the AZ cell walls, accounting for the higher force required for AZ tissue detachment to occur. Moreover, ethylene-induced flower abscission was accelerated in the RNAi lines and delayed in OEX lines, while exactly the opposite response was observed in the red ripe fruit AZs. This was partly attributed to alterations in the expression of cell wall hydrolases. Overall, these results indicate that P4Hs might regulate molecular and structural features of cell walls in the AZ as well as abscission progression by regulating the structure and function of AGPs.Sentence SummaryAlterations on the expression of tomato prolyl 4 hydroxylase 3 shifts the position of the pedicel abscission zone and alters ethylene induced abscission progression according to the developmental context of the pedicel.