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Samson, R.

Publications and source records attributed to Samson, R..

10 recordsLinked to original sources

Spatiotemporal remodeling of cytoskeletal and junction networks during somatic cell reprogramming

Summary/AbstractReprogramming somatic cells into induced pluripotent stem cells involves a dramatic reorganization of the cytoskeleton and junctions during the critical mesenchymal-to-epithelial transition stage. While protein abundance changes have been profiled, the spatiotemporal dynamics of protein-protein associations involving these structural components remain poorly resolved. Here, we present a time-resolved proximity proteomics resource that maps cytoskeletal and junctional remodeling across 27 baits during the early stages of reprogramming. We identified over 1100 high-confidence interactions, including many not previously reported, capturing the dynamic reorganization of cell architecture. By integrating proximity-dependent biotinylation with quantitative proteomics, we distinguished spatial relocalizations from abundance-driven effects. Dynamic redistributions of actin regulators and desmosomal proteins were observed, and a targeted short interfering RNA screen uncovered early acting structural proteins essential for colony formation. Our findings reveal adhesion and cytoskeletal maturation as structural bottlenecks in reprogramming and provide a broadly applicable framework for mapping subcellular remodeling during dynamic cell fate transitions.

systems biology↗

Quantum Cognition Machine Learning for Forecasting Chromosomal Instability

The accurate prediction of chromosomal instability from the morphology of circulating tumor cells (CTCs) enables real-time detection of CTCs with high metastatic potential in the context of liquid biopsy diagnostics. However, it presents a significant challenge due to the high dimensionality and complexity of single-cell digital pathology data. Here, we introduce the application of Quantum Cognition Machine Learning (QCML), a quantum-inspired computational framework, to estimate morphology-predicted chromosomal instability in CTCs from patients with metastatic breast cancer. QCML leverages quantum mechanical principles to represent data as state vectors in a Hilbert space, enabling context-aware feature modeling, dimensionality reduction, and enhanced generalization without requiring curated feature selection. QCML outperforms conventional machine learning methods when tested on out of sample verification CTCs, achieving higher accuracy in identifying predicted large-scale state transitions (pLST) status from CTC-derived morphology features. These preliminary findings support the application of QCML as a novel machine learning tool with superior performance in high-dimensional, low-sample-size biomedical contexts. QCML enables the simulation of cognition-like learning for the identification of biologically meaningful prediction of chromosomal instability from CTC morphology, offering a novel tool for CTC classification in liquid biopsy.

cancer biology↗

A novel Pbunavirus phage from the Ganges River in biocontrol of multidrug-resistant Pseudomonas aeruginosa in wastewater by downregulation of las/rhl systems and reduction of KPC carbapenemases

Wastewater systems are reservoirs of multidrug-resistant (MDR) pathogens, including Pseudomonas aeruginosa, mirroring those found in the hospital effluents. Effective treatment of raw sewage for MDR P. aeruginosa abatement is critical for safe effluent disposal. This study reports the isolation of a novel phage ({phi}PRS-1) within the Pbunavirus genus from a pristine stretch of the Ganges River, targeting the MDR strain of P. aeruginosa. Antibacterial and antibiofilm assays of {phi}PRS-1 against P. aeruginosa PAO1 demonstrated robust efficacy, achieving log10 reductions of 8.14 in planktonic cells, 9.83 in biofilm inhibition, and 7.01 in biofilm disruption after 24 hours. Additionally, {phi}PRS-1 effectively disrupted the preformed biofilm of various other MDR P. aeruginosa strains with >5 log10 reductions. Mechanistically, {phi}PRS-1 downregulated quorum-sensing genes and reduced the carbapenemase resistance KPC cluster, validated through qRT-PCR analysis. Evaluation of {phi}PRS-1 in raw sewage revealed a 4.2 log10 CFU/mL reduction in the P. aeruginosa counts, highlighting its efficacy in complex environmental matrices. In vitro, cytotoxicity assays confirmed the phages safety. The use of {phi}PRS-1 for tackling MDR P. aeruginosa in the wastewater offers a sustainable alternative, potentially reducing reliance on other treatment methods. The findings have attempted to deliver SDGs 3, 6, 11, 14, and 15. HighlightsO_LIA novel phage ({phi}PRS-1) from an untapped location of the Ganges River C_LIO_LI{phi}PRS-1 reduces planktonic cells of MDR P. aeruginosa by 8.14 log10 in 24 hours C_LIO_LIAntibiofilm potentials: 9.83 log10 reduction (inhibition) >5 log10 reduction (disruption) C_LIO_LIDownregulates quorum-sensing genes and reduces KPC resistance in MDR P. aeruginosa C_LIO_LI{phi}PRS-1 shows 4.2 log10 CFU/mL reduction of MDR P. aeruginosa in raw sewage C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=111 SRC="FIGDIR/small/621487v1_ufig1.gif" ALT="Figure 1"> View larger version (49K): org.highwire.dtl.DTLVardef@14f4ac0org.highwire.dtl.DTLVardef@b4a8d9org.highwire.dtl.DTLVardef@b97a6borg.highwire.dtl.DTLVardef@114072c_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

Characterization of a Novel Tequatrovirus Phage from Pristine Stretch of The Ganges River, India, in Reducing Bacterial Load from Sewage Water

Effective treatment of wastewater (WW) and its reuse is necessary to meet certain sustainable development goals and a circular economy. Escherichia coli is one of the primary contaminants in the WW, and its extra-intestinal occurrence poses a considerable threat under one health. This study is the first report of a novel broad-spectrum phage ([fe]ERS-1) isolated from a pristine stretch of the Ganges River in the biocontrol of E. coli, resistant to 3rd-and 4th generation cephalosporins and aztreonam. This is the first report of a phage from the Tequatrovirus genus to infect P. aeruginosa. The [fe]ERS-1 could reduce the abundance of E. coli cells by 8.22 log10 CFU/mL [≤]24 hrs. Additionally, {square} ERS-1 disrupted the biofilm of E. coli with a reduction of 3.88 log10 CFU/mL. Further, {square} ERS-1 could inhibit biofilm by multiple strains of E. coli and multiple genera (E. coli, S. boydii, and P. aeruginosa). The phage {square} ERS-1 reduced bacterial counts in raw WW by 2 log10 CFU/mL and 4 log10 CFU/mL reduction in coliform-enriched WW in [≤]24 hours. Overall, this study suggests that {square} ERS-1 could be used as an effective alternative to be combined with other treatments for improving the quality of WW disposal and environmental health by reducing the bacterial load. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=114 SRC="FIGDIR/small/621489v1_ufig1.gif" ALT="Figure 1"> View larger version (55K): org.highwire.dtl.DTLVardef@1020e4dorg.highwire.dtl.DTLVardef@1f8e4d3org.highwire.dtl.DTLVardef@176e4f0org.highwire.dtl.DTLVardef@b07465_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIIsolation of a novel phage from a pristine stretch of the Ganges River C_LIO_LIAntibiofilm activity against E. coli >8 log10 inhibition, >3 log10 disruption C_LIO_LIBiofilm inhibition of >50% against P. aeruginosa and S. boydii C_LIO_LI2 log10 and 4 log10 reduction of bacterial counts in phage-treated raw sewage C_LI

microbiology↗

TSC22D, WNK and NRBP gene families exhibit functional buffering and evolved with Metazoa for macromolecular crowd sensing

The ability to sense and respond to osmotic fluctuations is critical for the maintenance of cellular integrity. Myriad redundancies have evolved across all facets of osmosensing in metazoans, including among water and ion transporters, regulators of cellular morphology, and macromolecular crowding sensors, hampering efforts to gain a clear understanding of how cells respond to rapid water loss. In this study, we harness the power of gene co-essentiality analysis and genome-scale CRISPR-Cas9 screening to identify an unappreciated relationship between TSC22D2, WNK1 and NRBP1 in regulating cell volume homeostasis. Each of these genes have paralogs and are functionally buffered for macromolecular crowd sensing and cell volume control. Within seconds of hyperosmotic stress, TSC22D, WNK and NRBP family members physically associate into cytoplasmic biocondensates, a process that is dependent on intrinsically disordered regions (IDRs). A close examination of these protein families across metazoans reveals that TSC22D genes evolved alongside a domain in NRBPs that specifically binds to TSC22D proteins, which we have termed NbrT (NRBP binding region with TSC22D), and this co-evolution is concomitant with rapid IDR length expansion in WNK family kinases. Our study identifies functions for unrecognized components of the cell volume sensing machinery and reveals that TSC22D, WNK and NRBP genes evolved as cytoplasmic crowding sensors in metazoans to co-regulate rapid cell volume changes in response to osmolarity.

cell biology↗

Habitat amount, temperature and biotic interactions drive community structure, life-history traits, and performance traits of cavity-nesting bees and wasps and their natural enemies in cities

O_LIUrban ecosystems are associated with socio-ecological conditions that can filter and promote taxa. However, the strength of the effect of ecological filtering on biodiversity could vary among biotic and abiotic factors. Here, we investigate the effects of habitat amount, temperature, and host-enemy biotic interactions in shaping communities of cavity-nesting bees and wasps (CNBW) and their natural enemies. C_LIO_LIWe installed trap-nests in 80 sites distributed along urban intensity gradients in 5 European cities (Antwerp, Paris, Poznan, Tartu and Zurich). We quantified the species richness and abundance of CNBW hosts and their natural enemies, as well as two performance traits (survival and parasitism) and two life-history traits (sex ratio and number of offspring per nest for the hosts). We analysed the importance of the abiotic and biotic variables using generalized linear models and multi-model inference. C_LIO_LIWe found that habitat amount and temperature were the main drivers of CNBW host responses, with larger habitat amounts resulting in higher species richness and abundance, and a larger total number of brood cells per nest for both bees and wasps, as well as a larger probability of survival for bees. Conversely, higher local temperatures decreased species richness, abundance, survival rate, number of brood cells per nest, and proportion of females in CNBW hosts. C_LIO_LIBiotic interactions with natural enemies shaped wasp species richness, with higher levels of parasitism resulting in more wasp species. Similarly, our results showed direct density-dependence between CNBW hosts and their natural enemies. C_LIO_LIOverall, our study highlights the importance of habitat amount and temperature in shaping urban food webs, through direct effects on hosts responses and the subsequent consequences for their natural enemies. As cities prepare to tackle the future consequences of global change, strategies that make it possible to maintain available habitat and mitigate urban overheating emerge as a key urban adaptation for biodiversity conservation. C_LI

ecology↗

Compost Teas: market survey and microbial analysis

Compost teas (CTs) are fermented watery compost extracts that can be made with a wide variety of organic ingredients. These extracts are applied on plants to promote plant growth and increase protection against pathogens. Several studies have shown that the live micro-organisms present in these teas play an important role in plant protection. Still, our knowledge on the identity and functionality of bacterial communities in CTs remains limited. Moreover, CTs are a heterogeneous group, as various combinations of ingredients, fermentation parameters and application guidelines are possible and little is known on the current practices in commercially available products. Consequently, also the microbial communities in these commercially available CTs are unknown. Here, we surveyed 68 CTs on ingredients, claims and guidelines regarding preparation and application. This revealed that most products were sold in dried form which needed to be rehydrated by the customers. Moreover, kelp, humic acid, sugar and molasses, were common ingredients. Additionally, we investigated the bacterial communities of eight products, covering different ingredients and preparations, using sequencing and culture-based techniques. Bacterial communities were remarkably similar at genus level, with Pseudomonas, Massilia, Comamonas, Chryseobacterium, Brevundimonas and Acinetobacter as most prevalent genera. The genus Pseudomonas was more abundant in CTs that were prepared without aeration. Moreover, differences between liquid and dry products revealed the importance of formulation to secure the viability of the desired microbes. This study has given insight in common practices in CTs on the market, their microbial composition, and highlighted several discrepancies with current literature. ImportanceCompost teas are fermented watery compost extracts which are used in professional and amateur horticulture to promote plant growth and suppress plant diseases. Beneficial microbes present in these extracts are suggested to play an important role in the mode of action. However, little is known on the identity and functionality of the bacteria in compost teas. Moreover, compost teas are a heterogeneous group of products that can be made with numerous combinations of ingredient and fermentation parameters and little is known on current practices in products available on the market. Therefore, we surveyed these practices in 68 commercial products and for a subset of these, we explored their bacterial communities using both culture dependent and independent techniques. This study has unveiled the common practices on the market, their microbial communities, and highlighted several discrepancies between commercial practices and scientific research.

microbiology↗

Preclinical evaluation of a SARS-CoV-2 mRNA vaccine PTX-COVID19-B

Safe and effective vaccines are needed to end the COVID-19 pandemic caused by SARS-CoV-2. Here we report the preclinical development of a lipid nanoparticle (LNP) formulated SARS-CoV-2 mRNA vaccine, PTX-COVID19-B. PTX-COVID19-B was chosen among three candidates after the initial mouse vaccination results showed that it elicited the strongest neutralizing antibody response against SARS-CoV-2. Further tests in mice and hamsters indicated that PTX-COVID19-B induced robust humoral and cellular immune responses and completely protected the vaccinated animals from SARS-CoV-2 infection in the lung. Studies in hamsters also showed that PTX-COVID19-B protected the upper respiratory tract from SARS-CoV-2 infection. Mouse immune sera elicited by PTX-COVID19-B vaccination were able to neutralize SARS-CoV-2 variants of concern (VOCs), including the B.1.1.7, B.1.351 and P.1 lineages. No adverse effects were induced by PTX-COVID19-B in both mice and hamsters. These preclinical results indicate that PTX-COVID19-B is safe and effective. Based on these results, PTX-COVID19-B was authorized by Health Canada to enter clinical trials in December 2020 with a phase 1 clinical trial ongoing (ClinicalTrials.gov number: NCT04765436). One Sentence SummaryPTX-COVID19-B is a SARS-CoV-2 mRNA vaccine that is highly immunogenic, safe, and effective in preventing SARS-CoV-2 infection in mice and hamsters and is currently being evaluated in human clinical trials.

immunology↗

BOLD response to multiple grip forces in MS: going beyond the main effect of movement in BA 4a and BA 4p

This study highlights the importance of looking beyond the main effect of movement to study alterations in functional response in the presence of central nervous system pathologies such as multiple sclerosis (MS). Data show that MS selectively affects regional BOLD (Blood Oxygenation Level Dependent) responses to variable grip forces (GF). It is known that the anterior and posterior BA 4 areas (BA 4a and BA 4p) are anatomically and functionally distinct. It has also been shown in Healthy volunteers that there are linear (1st order, typical of BA 4a) and non-linear (2nd-4th order, typical of BA 4p) BOLD responses to different levels of GF applied during a dynamic motor paradigm. After modelling the BOLD response with a polynomial expansion of the applied GFs, the particular case of BA 4a and BA 4p were investigated in Healthy Volunteers (HV) and MS subjects. The main effect of movement (0th order) analysis showed that the BOLD signal is greater in MS compared to healthy volunteers within both BA 4 sub-regions. At higher order, BOLD-GF responses were similar in BA 4a but showed a marked alteration in BA 4p of MS subjects, with those with greatest disability showing the greatest deviations from the healthy response profile. Therefore, the different behaviour in HV and MS could only be uncovered through a polynomial analysis looking beyond the main effect of movement into the two BA 4 sub-regions. Future studies will investigate the source of this pathophysiology, combining the present fMRI paradigm with blood perfusion and non-linear neuronal response analysis.

neuroscience↗

A SARS-CoV-2 - host proximity interactome

Viral replication is dependent on interactions between viral polypeptides and host proteins. Identifying virus-host protein interactions can thus uncover unique opportunities for interfering with the virus life cycle via novel drug compounds or drug repurposing. Importantly, many viral-host protein interactions take place at intracellular membranes and poorly soluble organelles, which are difficult to profile using classical biochemical purification approaches. Applying proximity-dependent biotinylation (BioID) with the fast-acting miniTurbo enzyme to 27 SARS-CoV-2 proteins in a lung adenocarcinoma cell line (A549), we detected 7810 proximity interactions (7382 of which are new for SARS-CoV-2) with 2242 host proteins (results available at covid19interactome.org). These results complement and dramatically expand upon recent affinity purification-based studies identifying stable host-virus protein complexes, and offer an unparalleled view of membrane-associated processes critical for viral production. Host cell organellar markers were also subjected to BioID in parallel, allowing us to propose modes of action for several viral proteins in the context of host proteome remodelling. In summary, our dataset identifies numerous high confidence proximity partners for SARS-CoV-2 viral proteins, and describes potential mechanisms for their effects on specific host cell functions.

systems biology↗