Biology subjects

Elsayed, M.

Publications and source records attributed to Elsayed, M..

8 recordsLinked to original sources

bioRxiv2026

Lactate Receptor Activation Alleviates Senescence and Preserves Homeostasis of Aged Arteries

Arteries are among the first tissues to exhibit age-related dysfunction, yet the metabolic mechanisms driving vascular senescence remain poorly understood. Here, analysis of human aortic transcriptomic data identified HCAR1, encoding the lactate receptor GPR81, as one of the genes most significantly downregulated with age. We therefore investigated whether age-associated loss of GPR81 contributes to cellular senescence within the vessel wall. Senescent human endothelial cells and vascular smooth muscle cells accumulated neutral and oxidized lipids and exhibited increased labile iron and ferroptosis. Silencing GPR81 in early-passage cells recapitulated this metabolic phenotype together with multiple hallmarks of cellular senescence. Moreover, endothelial-specific deletion of GPR81 in young mice was sufficient to induce senescent cell accumulation, impaired lipid homeostasis, endothelial dysfunction, and elastin disorganization. Conversely, pharmacological activation of GPR81 with the agonist CHBA restored fatty acid metabolism, promoted glycolytic reprogramming, and attenuated ferroptotic stress and senescence-associated phenotypes. In lamin A knock-in (LAKI) progeroid mice, CHBA reduced arterial lipid accumulation and cellular senescence, shifted vascular cell composition toward a youthful state, improved endothelial integrity, and restored extracellular matrix homeostasis. Together, these findings identify age-associated loss of GPR81 as a driver of vascular metabolic dysfunction and cellular senescence and establish pharmacological GPR81 activation as a promising therapeutic strategy for preserving vascular homeostasis and mitigating age-associated cardiovascular disease.

bioengineering↗

bioRxiv2026

Cyclin B3-CDK1 couples translational de-repression to embryonic mitoses via OMA protein degradation in C. elegans.

During early embryogenesis, gene expression relies on maternally loaded mRNAs whose translation is controlled by RNA binding proteins. Here, we identify a critical role for the cyclin B3-CDK1 complex, known for its function in mitosis, in driving early embryonic gene expression in C. elegans. The cyclin B3-CDK1 complex works by marking the RNA binding OMA proteins (OMA-1 and OMA-2) for degradation, which ensures the de-repression and translation of their target mRNAs. OMA protein degradation relies on cyclin B3s conserved phosphate-binding pocket, which promotes multi-site OMA phosphorylation and the generation of phospho-degrons. Notably, the phosphate-binding pocket of cyclin B3 does not substantially contribute to its mitotic roles, indicating that the mitotic and translational functions of the cyclin B3-CDK1 complex are separable. These findings establish that embryonic activation of the cyclin B3-CDK1 complex drives both mitotic divisions and mRNA de-repression, which ensures that cell division is coupled to the early gene expression program in development.

developmental biology↗

bioRxiv2025

Facial Micro-Movements as a Proxy of Increasingly Erratic Heart Rate Variability While Experiencing Pressure Pain

The sensation of pain varies from person to person. These patterns of individual variations are difficult to capture using coarse subjective self-reports. However, they are important when prescribing therapies and tailoring them to the persons own sensations. Pain can be experienced differently by the same person, and fluctuate differently depending on the context, yet most analyses treat the problem under a one-size-fits-all model. In this work, we introduce a series of assays to objectively assess pressure pain across tasks with different motoric and cognitive demands, in relation to resting state. In a cohort of healthy individuals, we examine pain-free vs. pain states at rest, during drawing with heavy cognitive demands, during pointing to a visual target, and during a grooved peg task like inserting a grooved key in a matching grooved keyhole. We recorded Face videos, electrocardiographic signals and adopt a standardized data type called the micro-movement spikes (MMS) to characterize the biorhythmic activities of the Face micro-expressions and of the micro-fluctuations in the hearts inter beat interval timings. Using the MMS peaks, we find that the continuous Gamma family of probability distribution functions best fit the frequency histograms of both the Face and the heart data. Further, we find that the Gamma shape and scale parameters in both signals span a scaling power law whereby as the noise- to-signal ratio (Gamma scale parameter) increases, so does the randomness of the stochastic process (the Gamma shape decreases towards the memoryless exponential range). We find that as the heart IBI turns more erratic (noisier and more random) the facial ophthalmic region increases the noise and randomness too, with higher linear correlation for tasks requiring haptic feedback (R2 0.84) than for tasks requiring higher cognitive and memory loads (R2 0.77). Increases in transfer entropy shows that recent past activity ([~]167ms back) of the heart IBI and Face combined lower the uncertainty in the prediction of the present ophthalmic-Face activity, suggesting that this Face region may serve as a proxy of an increasingly dysregulated heart. These results bear implications for the detection and monitoring of pressure pain and heart dysregulated states. Scope StatementThis work uncovers personalized thresholds of pain through the combination of the participants fluctuations in HRV and facial micro-expressions. These signals are obtained before and after experiencing the sensation of pressure pain compared to a pain-free control condition. Tasks with higher haptic demand evoke higher differentiation in the signals than tasks with higher cognitive and memory loads. As the detection and tracking of such individual thresholds is possible through these unobtrusive and highly scalable methods, the work has implications for the personalized tailoring of pain treatments beyond the realms of the lab.

neuroscience↗

bioRxiv2025

Deep learning using structural MRI massively improves prediction accuracy of body mass index

Obesity is a major public health problem globally and there is considerable interest in the neural mechanisms in food overconsumption. Artificial intelligence (AI), particularly machine learning, has shown promise in characterizing links between brain morphometry and obesity. In 1106 adults, compared to other forms of machine learning, deep learning using 3D convolutional neural networks (3D-CNN) dramatically improves prediction of body mass index (BMI). The 3D-CNN model robustly predicted BMI (R2 =.325), outperforming random forest, elastic net, and tabnet models (R2s<.07) in a lockbox sample. Explainable AI analyses revealed the specific brain regions implicated and these regions were moderately associated with delay discounting, fluid cognition, gait speed, dexterity, and alcohol use. Collectively, these findings reveal the value of deep learning for understanding of the neural basis and motivational processes in the neurobiology of obesity.

neuroscience↗

bioRxiv2023

Intra-ocular Predation of Fluoroquinolone-Resistant Pseudomonas aeruginosa and Serratia marcescens by the Predatory Bacteria

Endogenous endophthalmitis caused by Gram-negative bacteria is an intra-ocular infection that can rapidly progress to irreversible loss of vision. While most endophthalmitis isolates are susceptible to antibiotic therapy, the emergence of resistant bacteria necessitates alternative approaches to combat intraocular bacterial proliferation. In this study the ability of predatory bacteria to limit intraocular growth of Pseudomonas aeruginosa, Serratia marcescens, and Staphylococcus aureus was evaluated in a New Zealand White rabbit endophthalmitis prevention model. Predatory bacteria Bdellovibrio bacteriovorus and Micavibrio aeruginosavorus were able to reduce proliferation of keratitis isolates of P. aeruginosa and S. marcescens. However, it was not able to significantly reduce S. aureus, which is not a productive prey for these predatory bacteria, suggesting that the inhibitory effect on P. aeruginosa requires active predation rather than an antimicrobial immune response. Similarly, UV-inactivated B. bacteriovorus were unable to prevent proliferation of P. aeruginosa. Together, these data suggest in vivo predation of Gram-negative bacteria within the intra-ocular environment.

microbiology↗

bioRxiv2023

Predatory Bacteria can Reduce Pseudomonas aeruginosa Induced Corneal Perforation and Proliferation in a Rabbit Keratitis Model

PurposePseudomonas aeruginosa keratitis is a severe ocular infection that can lead to perforation of the cornea. In this study we evaluated the role of bacterial quorum sensing in generating corneal perforation and bacterial proliferation and tested whether co-injection of the predatory bacteria Bdellovibrio bacteriovorus could alter the clinical outcome. P. aeruginosa with lasR mutations were observed among keratitis isolates from a study collecting samples from India, so an isogenic lasR mutant strain of P. aeruginosa was included. MethodsRabbit corneas were intracorneally infected with P. aeruginosa strain PA14 or an isogenic {Delta}lasR mutant and co-injected with PBS or B. bacteriovorus. After 24 h, eyes were evaluated for clinical signs of infection. Samples were analyzed by scanning electron microscopy, optical coherence tomography, sectioned for histology, and corneas were homogenized for CFU enumeration and for inflammatory cytokines. ResultsWe observed that 54% of corneas infected by wild-type PA14 presented with a corneal perforation (n=24), whereas only 4% of PA14 infected corneas that were co-infected with B. bacteriovorus perforate (n=25). Wild-type P. aeruginosa proliferation was reduced 7-fold in the predatory bacteria treated eyes. The {Delta}lasR mutant was less able to proliferate compared to the wild-type, but was largely unaffected by B. bacteriovorus. ConclusionThese studies indicate a role for bacterial quorum sensing in the ability of P. aeruginosa to proliferate and cause perforation of the rabbit cornea. Additionally, this study suggests that predatory bacteria can reduce the virulence of P. aeruginosa in an ocular prophylaxis model.

microbiology↗

bioRxiv2022

Breakdown of cooperative architecture in dual species biofilms and the spatial ecology of predation

Adherence to surfaces and secretion of extracellular matrix, or biofilm formation, is common in the microbial world, but we often do not know how interaction at the cellular spatial scale translates to higher-order biofilm community ecology. Here we explore an especially understudied element of biofilm ecology, namely predation by the bacterium Bdellovibrio bacteriovorus. This predator can kill and consume many different Gram-negative bacteria, including Vibrio cholerae and Escherichia coli. V. cholerae can protect itself from predation within highly packed biofilm structures that it creates, whereas E. coli biofilms are highly susceptible to B. bacteriovorus. Here we explore how predator-prey dynamics change when V. cholerae and E. coli are growing in biofilms together. We find that in dual species prey biofilms, E. coli survival under B. bacteriovorus predation increases, whereas V. cholerae survival decreases. E. coli benefits from predator protection when it becomes embedded within expanding groups of highly packed V. cholerae. But we also find that the ordered, highly packed, and clonal biofilm structure of V. cholerae can be disrupted if V. cholerae cells are directly adjacent to E. coli cells at the start of biofilm growth. When this occurs, the two species become entangled, and the resulting disordered cell groups do not block predator entry. Because biofilm cell group structure depends on initial cell distributions at the start of prey biofilm growth, the colonization dynamics have a dramatic impact on the eventual multispecies biofilm architecture, which in turn determines to what extent both species survive exposure to B. bacteriovorus. Significance StatementBacteria live in multispecies, spatially structured communities ubiquitously in the natural world. These communities, or biofilms, have a strong impact on microbial ecology, but we often do not know how cellular scale interactions determine overall biofilm structure and community dynamics. Here we explore this problem in the context of predator-prey interaction, with two prey species - Vibrio cholerae and Escherichia coli - being attacked by the bacterial predator Bdellovibrio bacteriovorus. We find that when V. cholerae and E. coli grow together in biofilms, the architectures that they both produce change in ways that cannot be predicted from looking at each prey species alone, and that these changes in cell group structure impact the community dynamics of predator-prey interaction in biofilms.

microbiology↗

bioRxiv2020

Predation by Bdellovibrio bacteriovorus transforms the landscape and community assembly of bacterial biofilms

The predatory bacterium Bdellovibrio bacteriovorus follows a life cycle in which it attaches to the exterior of a Gram-negative prey cell, enters the periplasm, and harvests resources to replicate before lysing the host to find new prey. Predatory bacteria such as this are common in many natural environments, as are groups of matrix-bound clusters of prey cells, termed biofilms. Despite the ubiquity of both predatory bacteria and biofilm-dwelling prey, the interaction between B. bacteriovorus and prey cells inside biofilms has received little attention and has not yet been studied at the micrometer scale. Filling this knowledge is critical to understanding the nature of predator-prey interaction in nature. Here we show that B. bacteriovorus is able to prey upon biofilms of the pathogen Vibrio cholerae, but only up until a critical maturation threshold past which the prey biofilms are protected from their predators. We determine the contribution of matrix secretion and cell-cell packing of the prey biofilm toward this protection mechanism. Our results demonstrate that B. bacteriovorus predation in the context of this protection threshold fundamentally transforms the sub-millimeter scale landscape of biofilm growth, as well as the process of community assembly as new potential biofilm residents enter the system.

microbiology↗