Biology subjects

Diouf, D.

Publications and source records attributed to Diouf, D..

6 recordsLinked to original sources

bioRxiv2026

ST3GAL3 loss-of-function disrupts synaptic integrity and excitatory/inhibitory cortical dynamics

This study examined the role of ST3GAL3 as a regulator of excitatory/inhibitory (E/I) synaptic homeostasis using a human iPSC-based model. Neurodevelopmental disorders (NDDs) are increasingly linked to disruptions in the E/I balance, yet the molecular determinants remain poorly defined. ST3GAL3, a sialyltransferase associated with both rare monogenic disorders, including intellectual disability and infantile epilepsy, and complex polygenic conditions, such as ADHD, represents a strong candidate gene for involvement in synaptic regulation. To investigate this, isogenic ST3GAL3 knockout (ST3GAL3 KO) and wildtype (WT) iPSC lines were generated through CRISPR/Cas9 editing and differentiated into cortical neurons using both directed and induced protocols. This dual strategy enabled robust comparisons across cellular contexts and minimised methodological bias. To this end, we conducted functional characterisation using microelectrode array (MEA) technology alongside transcriptomic profiling through RNA sequencing (RNAseq), directly comparing ST3GAL3 KO-derived neurons with their isogenic controls. Functional assays using MEA revealed aberrant bursting patterns, particularly prolonged burst durations and heightened variability in S3GAL3KO neurons. Complementary transcriptomic profiling performed via RNAseq demonstrated downregulation in ST3GAL3 KO lines of genes involved in cognition, memory, as well as glutamatergic and GABAergic synaptic plasticity and functionality, providing molecular evidence for widespread synaptic dysregulation. Together, these findings establish ST3GAL3 as a key regulator of E/I balance in the cortices, advancing current knowledge on the pathophysiological involvement of ST3GAL3 deficiencies in the development of NDDs.

neuroscience↗

bioRxiv2026

A stable genomic variant for photoperiodic flowering plasticity to enhance grain mold escape and yield stability in sorghum

Grain mold severely constrains sorghum [Sorghum bicolor (L.) Moench] productivity and grain quality in subhumid environments. Photoperiod-sensitive flowering plays a key role in mold avoidance and yield stability along north-south rainfall gradients. In response to the high susceptibility of elite cultivars in subhumid zones of Senegal, we developed and characterized a recombinant inbred line (RIL) population derived from Nganda (grain mold-susceptible) and Grinkan (photoperiod-sensitive) varieties. The population was evaluated across three distinct agro-ecological zones over two years. Environmental indices derived from genotype-environmental interactions, together with defined growth windows, strongly influenced flag leaf appearance (FLA), a photoperiodic flowering trait. Plasticity parameters (intercept and slope) for environmental indices, FLA, grain mold severity, and yield enabled identification of loci contributing to flowering response, mold resistance, and yield stability. The maturity gene Ma1 and two QTLs for FLA, qFLA6.2 and qFLA6.3, were identified, stable across environments, and colocalized with grain mold and yield QTLs. The wild-type Ma1 allele from Grinkan delayed FLA and reduced grain mold damage but was not associated with increased yield. The Ma1 effect was confirmed using the developed breeder-friendly KASP marker, Sbv3.1_06_40312464K, in 174 F3 three-way cross families. Photoperiod-sensitive lines with intermediate-to-late FLA alleles showed strong negative associations with mold damage. Overall, the identified stable loci and candidate lines provide foundations for effective molecular breeding of climate-resilient varieties. PLAIN LANGUAGE SUMMARYGrain mold is a fungal disease that reduces sorghum grain yield and quality, particularly in subhumid climates. With the limited number of resistant elite varieties, photoperiod-sensitive flowering to day length variation can contribute to grain mold escape at the end of rainy seasons. We characterized 286 sorghum recombinant inbred lines across three contrasting environments over two years along rainfall gradients in Senegal. Using flag leaf appearance (FLA), which is a photoperiodic flowering trait, strong genotype-environment interactions for FLA and genotypic plasticity were revealed. We identified and validated the common genomic locus associated with FLA variation and its plasticity across environments, the canonical maturity gene Ma1, which was influenced by temperature variation across environments. The presence of Ma1 in the background of photoperiod-sensitive lines enhances grain mold avoidance and yield stability along rainfall gradients in Senegal. CORE IDEASO_LIWe investigated photoperiodic flowering plasticity in sorghum as a contributor to grain mold resistance and yield stability along rainfall gradients. C_LIO_LIThe Maturity locus Ma1 (qFLA6.1) is the major contributor of photoperiodic flowering and its plasticity across semi-arid and subhumid environments. C_LIO_LIHybrid genotypes carrying two stable loci qFLA6.1 and qFLA6.2 sustain high grain mold avoidance in diverse environments. C_LIO_LIPhotoperiod-sensitive lines with medium to late flowering times are effective in avoiding grain mold, while maintaining yield stability in subhumid regions. C_LI

genetics↗

bioRxiv2024

Upregulation of the Proto-Oncogene Src Kinase in Alzheimer's Disease: From Molecular Interactions to Therapeutic Potential

Alzheimers disease (AD) is a progressive neurodegenerative disease, resulting in an irreversible deterioration of multiple brain regions associated with cognitive dysfunction. Phosphorylation of the microtubule-associated protein, Tau, is known to occur decades before symptomatic AD. The Src family of tyrosine kinases are known to phosphorylate select tyrosine sites on Tau and promote microtubule disassembly and subsequent neurofibrillary tangle (NFT) formation. Our data show that the proto-oncogene, non-receptor tyrosine kinase Src colocalizes with a range of late (PHF1) to early (MC1) AD-associated phosphorylated Tau epitopes. The strongest co-occurrence is seen with MC1 (probability of MC1 given Src =100%), an early AD-specific conformational dependent epitope. Single-cell RNA sequencing data of 101 subjects show that Src is upregulated in both AD inhibitory and excitatory neurons. The most significantly affected, by orders of magnitude, were excitatory neurons which are the most prone to pathological Tau accumulation. We measured Src phosphorylation by mass spectrometry across a cohort of 48 patient neocortical tissues and found that Src has increased phosphorylation on Ser75, Tyr187, and Tyr440 in AD, showing that Src kinase undergoes distinct phosphorylation alterations in AD. Through Brownian dynamics simulations of Src and Tau, we show that as Tau undergoes the transition into disease-associated paired helical filaments, there is a notable seven-fold increase in Src contact with Tau. These results collectively emphasize Src kinases central role in Tau phosphorylation and its close association with Tau epitopes, presenting a promising target for potential therapeutic intervention.

neuroscience↗

bioRxiv2019

Influence of plant genotype and soil on the wheat rhizosphere microbiome: identification of a core microbiome across eight African and European soils

Here, we assessed the relative influence of wheat genotype, agricultural practices (conventional vs organic) and soil type on the rhizosphere microbiome. We characterized the prokaryotic (archaea, bacteria) and eukaryotic (fungi, protists) communities in soils from four different countries (Cameroon, France, Italy, Senegal) and determined if a rhizosphere core microbiome existed across these different countries. The wheat genotype had a limited effect on the rhizosphere microbiome (2% of variance) as the majority of the microbial taxa were consistently associated to multiple wheat genotypes grown in the same soil. Large differences in taxa richness and in community structure were observed between the eight soils studied (57% variance) and the two agricultural practices (10% variance). Despite these differences between soils, we observed that 179 taxa (2 archaea, 104 bacteria, 41 fungi, 32 protists) were consistently detected in the rhizosphere, constituting a core microbiome. In addition to being prevalent, these core taxa were highly abundant and collectively represented 50% of the reads in our dataset. Based on these results, we identify a list of key taxa as future targets of culturomics, metagenomics and wheat synthetic microbiomes. Additionally, we show that protists are an integral part of the wheat holobiont that is currently overlooked. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=126 SRC="FIGDIR/small/777383v2_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@dd56a6org.highwire.dtl.DTLVardef@163b5f7org.highwire.dtl.DTLVardef@13f6bd7org.highwire.dtl.DTLVardef@c10d9d_HPS_FORMAT_FIGEXP M_FIG C_FIG

ecology↗

bioRxiv2018

The contrasting response to drought and waterlogging is underpinned by divergent DNA methylation programs associated with gene expression in sesame

DNA methylation is a heritable epigenetic mechanism that participates in gene regulation under abiotic stresses in plants. Sesame (Sesamum indicum L.) is typically considered a drought-tolerant crop but highly susceptible to waterlogging, a property attributed to its presumed origin in Africa or India. Understanding DNA methylation patterns in sesame under drought and waterlogging conditions can provide insights into the regulatory mechanisms underlying its contrasting responses to these principal abiotic stresses. Here, we combined Methylation-Sensitive Amplified Polymorphism and transcriptome analyses to profile cytosine methylation patterns, gene expression alteration, and their interplay in drought-tolerant and waterlogging-tolerant sesame genotypes under control, stress and recovery conditions. Our data showed that drought stress strongly induced de novo methylation (DNM) whereas most of the loci were demethylated (DM) during the recovery phase. In contrast, waterlogging decreased the level of methylation under stress but during the recovery phase, both DM and DNM were concomitantly deployed. In both stresses, the differentially expressed genes (DEGs) were highly correlated with the methylation patterns. We observed that DM was associated with the up-regulation of the DEGs while DNM was correlated with the down-regulation of the DEGs. In addition, we sequenced 44 differentially methylated regions of which 90% overlapped with the promoters and coding sequences of the DEGs. Altogether, we demonstrated that sesame has divergent epigenetic programs that respond to drought and waterlogging stresses. Our results also highlighted the possible interplay among DNA methylation and gene expression, which may modulate the contrasting responses to drought and waterlogging in sesame.

plant biology↗

bioRxiv2017

Bayesian estimation of MSM population size in Côte d’Ivoire

Cote dIvoire has one of the largest HIV epidemics in West Africa with around half million people living with HIV. Key populations like gay men and other men who have sex with men (MSM) are often disproportionately burdened with HIV due to specific acquisition and transmission risks. Quantifying the MSM population sizes at subnational level is critical to improving the HIV prevention interventions. While survey-based direct estimates of MSM numbers are available at a few urban centers in C{circumflex}ote dIvoire, no data on MSM population size exists at other areas without any community infrastructure to facilitate sufficient access to the MSM community. We use this limited data in a Bayesian regression setup to produce first empirically calculated estimates of the numbers of MSM in all areas of C{circumflex}ote dIvoire prioritized in the HIV response. Our hierarchical model imputes missing covariates using geospatial information and allows for proper uncertainty quantification leading to meaningful confidence bounds for the predicted MSM population size estimates. The intended impact of this process is to increase uptake and use of high quality, comprehensive epidemiologic and interventional data in program planning. These estimates will help design future surveys and support the planning of the scale and content of HIV prevention and treatment programs for MSM in C{circumflex}ote dIvoire.

epidemiology↗