Biology subjects

Sallard, E.

Publications and source records attributed to Sallard, E..

5 recordsLinked to original sources

bioRxiv2026

Topographical differences during motion processing in autistic and dyslexic children

Atypical motion processing has been reported in multiple developmental conditions, including autism and dyslexia, and taken as support for a general developmental vulnerability in the dorsal stream. Yet by uncovering dynamically unfolding processes, electroencephalography can determine the extent to which motion processing signatures are shared or distinct across different developmental conditions. Here we used pre-registered topographical analyses across the whole high-density electrode array to determine, for the first time, whether autistic and dyslexic children activate the same or distinct brain pathways as typically developing children, when completing two motion processing tasks. Participants were 29 autistic, 44 dyslexic and 57 typically developing children aged 6 to 14 years. Group differences in overall brain response strength were found in both tasks. Topographical activity differed in both autistic and dyslexic children compared to typically developing children (but not between autistic and dyslexic children) in a motion coherence task between 456 - 560 ms. However, group differences in a direction integration task (with no incoherent motion) depended on stimulus difficulty and time window (434 - 500 ms and 538 - 638 ms), with different patterns of divergence from typical development in autism and dyslexia. These results suggest that there are differences in the brain networks used to accomplish motion processing tasks in both autistic and dyslexic children, and demonstrate the utility of a topographical approach for detecting group differences in neural mechanisms, which can be missed by univariate approaches. Key pointsO_LIWe use an electrical neuroimaging approach to provide new insights into the neural mechanisms of motion processing in autism and dyslexia C_LIO_LIAutistic and dyslexic children both differed from typically developing children in the strength and topography of their brain responses. C_LIO_LIMotion processing activates atypical brain networks in both autistic and dyslexic children. C_LI

neuroscience↗

bioRxiv2023

ADEVO: Proof-of-concept of Adenovirus Directed EVOlution by random peptide display on the fiber knob

Directed evolution of viral vectors involves the generation of randomized libraries followed by artificial selection of improved variants. Directed evolution only yielded limited results in adenovirus vector (AdV) development until now, mainly due to insufficient complexities of randomized libraries. Clinical applications of AdVs as gene therapy or oncolytic vectors are still hampered by the predetermined tropism of natural types. To overcome this challenge, we hypothesized that the technology of randomized peptide insertions on the capsid surface can be incorporated into the AdV bioengineering toolbox for vector retargeting. Here we developed Adenovirus Directed EVOlution (ADEVO) protocols based on fiber knob peptide display. As a proof-of-concept, HAdV-C5-derived libraries were constructed following three distinct protocols and selected on A549-DCAR cells that lack the HAdV-C5 primary receptor, with the goal of identifying variants able to infect and lyse these tumor cells more efficiently. All protocols enabled the construction of high complexity libraries with up to 9.6x10^5 unique variants, an approximate 100-fold improvement compared to previously published AdV libraries. After selection, the most enriched variants did not display enhanced infectivity but rather more efficient replication and cell lysis. This warrants investigations into potential unsuspected involvement of the fiber protein in adenovirus replication. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=145 SRC="FIGDIR/small/567388v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@187f7baorg.highwire.dtl.DTLVardef@1990555org.highwire.dtl.DTLVardef@12d3c60org.highwire.dtl.DTLVardef@d703da_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2023

Combining CRISPR/Cas mediated terminal resolution with a novel genetic workflow to achieve high diversity adenoviral libraries

While recombinant Adenoviruses (rAds) are widely used in both laboratory and medical gene transfer, library-based applications using this vector platform are not readily available. Recently, we developed a new method, the CRISPR/Cas9 mediated in vivo terminal resolution (CTR) aiding high efficiency rescue of rAds from recombinant DNA. Here we report on a genetic workflow that allows construction of BAC-based rAd-libraries employing the efficiency of CTR. We utilized frequent, pre-existing genomic sequences to allow insertion of a selection marker, complementing two selected target sites into novel endonuclease recognition sites. In a second step, this selection marker is replaced with a transgene or mutation of interest via Gibson assembly. Our approach does not cause unwanted genomic off-target mutations while providing substantial flexibility for the site and nature of the genetic modification. This new genetic workflow, which we termed half-site directed fragment replacement (HFR) allows introduction of >106 unique modifications into rAd encoding BACs using laboratory scale methodology. To demonstrate the power of HFR, we rescued barcoded viral vector libraries yielding a diversity of [~]2.5x104 modified rAd per cm2 of transfected cell culture. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=141 SRC="FIGDIR/small/566979v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@1db61a7org.highwire.dtl.DTLVardef@1e85764org.highwire.dtl.DTLVardef@c17178org.highwire.dtl.DTLVardef@a299_HPS_FORMAT_FIGEXP M_FIG C_FIG

synthetic biology↗

bioRxiv2022

Adenovirus type 34 and HVR1-deleted Adenovirus type 5 do not bind to PF4: clearing the path towards vectors without thrombosis risk

The adenoviral vector based AstraZeneca and Janssen COVID vaccines have been associated with rare cases of thrombosis, a condition which depends on adenovirus binding to the blood protein Platelet Factor 4 (PF4). In order to identify adenoviruses with low or absent affinity for PF4, we screened dozens of types from various adenovirus species, and Adenovirus type 5 (Ad5) derived vectors carrying genetic or chemical modifications of different hexon hyper-variable regions (HVR). For this purpose, we established an armamentarium of techniques including ELISA-qPCR and Aggregate Pull-Down (APD), which enabled fast and sensitive assessments of virus-protein interactions. Unlike most tested serotypes, Ad34 did not bind to PF4. Likewise, the deletion or shielding of the HVR1 loop of Ad5 seemingly ablated its PF4 binding. Therefore, we showed that PF4 binds to adenovirus hexon through interactions dependent on HVR1, and identified vectors that may avoid or decrease the risk of thrombosis and represent safer candidates for vaccine or gene therapy vector development.

microbiology↗

bioRxiv2018

Differential brain mechanisms of selection and maintenance of information during working memory

Working memory is our ability to select and temporarily hold information as needed for complex cognitive operations. The temporal dynamics of sustained and transient neural activity supporting the selection and holding of memory content is not known. To address this problem, we recorded magnetoencephalography (MEG) in healthy participants performing a retro-cue working memory task in which the selection rule and the memory content varied independently. Multivariate decoding and source analyses showed that selecting the memory content relies on prefrontal and parieto-occipital persistent oscillatory neural activity. By contrast, the memory content was reactivated in a distributed occipito-temporal posterior network, preceding the working memory decision and in a different format that during the visual encoding. These results identify a neural signature of content selection and characterize differentiated spatiotemporal constraints for subprocesses of working memory.

neuroscience↗