Biology subjects

Williams, A.

Publications and source records attributed to Williams, A..

At least 37 records · Page 2Linked to original sources

bioRxiv2025

Transglutaminase 2 predicts parasitic worm-mediated protection against hepatic steatosis in obese mice

Parasitic worm infection can mitigate high fat diet-induced chronic inflammation in obese mice by reducing hepatic fat accumulation and improving insulin sensitivity. However, the molecular alterations during infection-mediated regulation of hepatic steatotic events in obesity remain poorly understood. Here, we integrated proteomic and metabolomic analyses of infected obese mice, a functional deworming and interleukin-4c (IL-4c) treated animal model, and an obese patient cohort before and after bariatric surgery to uncover molecular targets/pathways indicative of the regulation of hepatic steatosis by gut Heligmosomoides polygyrus bakeri (H. p. bakeri) helminth infection. Proteomic analysis identified alterations in several molecules related to metabolism and showed elevated levels of transglutaminase 2 (TGM2) proportionate with an infection-regulated lipid load in diet-induced obese (DIO) mice. The role of TGM2 as a reliable predictor of hepatic steatosis was validated using deworming experiments which revealed a decrease in the liver tissue levels of Tgm2 following removal of H. p. bakeri. Further validation showing increase in Tgm2 levels in IL-4c treated mice confirmed its relevance as a general response indicator of type 2 immune response induced by helminth infection. Assessment of circulating TGM2 levels in matched obese patients before and after bariatric surgery revealed no change, indicating that differential expression of TGM2 is a unique functional response to regulation of hepatic steatosis by H. p. bakeri infection. Together, our data show that TGM2 is a unique predictive marker of improvement in hepatic lipid profile and provides additional evidence that parasitic worm infection protects against hepatic steatosis in DIO mice. These findings pave the way for novel therapeutic opportunities to resolve hepatic steatosis and prevent its progression to severe forms of metabolic dysfunction-associated steatotic liver disease, based on TGM2 coupled with mimetics of H. p. bakeri-derived products. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=138 SRC="FIGDIR/small/689654v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@1cae718org.highwire.dtl.DTLVardef@9ec0aorg.highwire.dtl.DTLVardef@1679b1corg.highwire.dtl.DTLVardef@f86bc9_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2025

Synergistic therapeutic effects of endolysin BNT331 and a Lactobacillus crispatus consortium in a human vagina chip model of bacterial vaginosis

Bacterial vaginosis (BV) is a vaginal infection caused by an imbalance in the vaginal microbiome characterized by a decrease in healthy bacteria dominated by Lactobacillus crispatus along with a concomitant increase in dysbiotic bacteria, such as Gardnerella. Current treatments commonly fail to fully eradicate BV, and the lack of more effective therapies is due in part to the absence of relevant human models. Here, we used a human vagina-on-a-chip (Vagina Chip) microfluidic culture device that has been previously shown to faithfully recapitulate the human vaginal microenvironment as well as the inflammatory and injurious effects of G. vaginalis to test the therapeutic efficacy of a consortium of L. crispatus alone or in combination with endolysin BNT331, which specifically targets and lyses Gardnerella. These studies revealed that when L. crispatus was added alone, it suppressed inflammation even though it failed to engraft or displace the G. vaginalis bacteria. In contrast, BNT331 effectively killed Gardnerella in dysbiotic Vagina Chip. Importantly, the combined administration of both treatments resulted in restoration of a healthier vaginal microenvironment, as indicated by higher engraftment of L. crispatus on-chip, inhibition of G. vaginalis, and a reduction in inflammation. Similar effects of this combined treatment were observed when administered to Vagina Chips infected with vaginal swab samples from BV patients. These data suggest that combination of a live biotherapeutic product composed of a L. crispatus consortium with a potent antimicrobial agent that targets G. vaginalis, such as BNT331, may offer an effective therapeutic strategy for patients with BV. One Sentence SummaryEndolysin BNT331 combined with Lactobacillus crispatus reduces bacterial load and suppresses inflammation in a human vagina chip model of bacterial vaginosis.

pathology↗

bioRxiv2025

PHO2 suppresses arbuscular mycorrhizal symbiosis in high phosphate conditions

Arbuscular mycorrhizal (AM) symbiosis is an ancient relationship formed between most plants and Glomeromycotina fungi, typically in response to phosphate (Pi) limitation in soils. By hosting these fungi in their roots, plants extend their access to essential mineral nutrients and water beyond the rhizosphere, while providing the fungus with carbon in return. This mutualistic symbiosis presents a promising tool for enhancing sustainability in agriculture, as it not only supports plant nutrition but also immunity and wider soil health. However, achieving high crop yields currently relies on supplementing plants with excess Pi, which suppresses AM symbiosis. We found that this suppression is mediated by a key negative regulator of the Pi starvation response (PSR) in rice (Oryza sativa), Phosphate overaccumulator 2 (PHO2). PHO2 encodes an E2 ubiquitin-conjugating enzyme which targets various proteins involved in the PSR in Pi-sufficient conditions for protein degradation. Here we report that pho2 mutants of rice and Nicotiana benthamiana retained high AM fungal colonisation even in high Pi conditions. Our transcriptomic analysis of uninoculated rice roots revealed that pho2 mutants are less sensitive to Pi treatment and retain susceptibility to AM symbiosis by maintaining expression of a core set of AM-related genes gating the early stage AM fungal entry, such as genes involved in strigolactone biosynthesis, LysM-containing plant receptors for fungal molecules, and components of the common symbiosis signalling pathway (CSSP). Furthermore, isotope tracing using 33P and phosphate transporter (PHT1) gene expression patterns collectively suggest enhanced direct and symbiotic Pi overaccumulation in pho2 mutant leaves. Together, our data reveal a new role for PHO2, as a negative regulator of AM colonisation and symbiotic Pi accumulation in shoots.

plant biology↗

bioRxiv2025

Profibrotic monocyte-derived alveolar macrophages as a biomarker and therapeutic target in systemic sclerosis-associated interstitial lung disease

Interstitial lung disease (ILD) is present in over 60% of patients with systemic sclerosis (SSc) and is the leading cause of SSc-related deaths. Profibrotic monocyte-derived alveolar macrophages (MoAM) play a causal role in the pathogenesis of pulmonary fibrosis in animal models where their persistence in the niche requires signaling through Colony Stimulating Factor 1 Receptor (CSF1R). We hypothesized that the presence and proportion of MoAM in bronchoalveolar lavage (BAL) fluid from patients with SSc-ILD may be a biomarker of ILD severity. To test this hypothesis, we analyzed BAL fluid from 9 prospectively enrolled patients with SSc-ILD and 13 healthy controls using flow cytometry and single-cell RNA sequencing. Patients with SSc-ILD had more MoAM and interstitial macrophages in BAL fluid than healthy controls, and their abundance was associated with lung fibrosis severity. We identified changes in the MoAM transcriptome as a function of treatment with mycophenolate, an effective therapy for SSc-ILD. In SSc-ILD lung explants, spatial transcriptomics identified an expanded population of interstitial macrophages spilling into the alveolar space. Our findings suggest that the proportion of profibrotic MoAM and interstitial macrophages in BAL fluid may serve as a biomarker of SSc-ILD and credential them as possible targets for therapy.

immunology↗

bioRxiv2025

SOX2 utilizes FOXA1 as a heteromeric transcriptional partner to drive proliferation in therapy-resistant prostate cancer

Treatment options and diagnostic outlook for men with advanced, therapy resistant prostate cancer (PCa) are extremely poor; this is primarily due to the common lack of durable response to androgen receptor (AR) targeted therapies and phenotypic transdifferentiation into a particularly lethal subtype known as neuroendocrine prostate cancer (NEPC). In this study, we mechanistically determine that SOX2 (a transcription factor originally repressed by AR) physically binds and acts in a concerted manner with FOXA1 (a key AR pioneering cofactor) to regulate a subset of genes which promote cell cycle progression, and lineage plasticity in AR-refractory prostate cancers. Our findings assert the SOX2/FOXA1 interaction as an important mediator of resistance to AR-targeted therapy and a driver of NEPC and lineage plasticity; their coordinated action and downstream signaling offers a potential novel therapeutic opportunity in late-stage PCa.

cancer biology↗

bioRxiv2025

Aberrant placental structure is corrected with repeated nanoparticle-mediated IGF1 treatments in a guinea pig model of fetal growth restriction

Fetal growth restriction (FGR) is most commonly due to placental insufficiency. There are currently no treatments for placental insufficiency or FGR, and the only intervention is iatrogenic pre-term delivery. We have previously shown efficacy of repeated placental nanoparticle-mediated insulin-like 1 growth factor (IGF1) treatment in improving placental efficiency (increased fetal-placental weight ratio) and correcting fetal growth in a maternal nutrient restriction (MNR) guinea pig model of FGR. Here we investigate the structural remodeling of the placenta following 3 repeated intraplacental injections of nanoparticle-mediated hIGF1 that may underpin the published improvements in placental efficiency and fetal growth. We hypothesize placenta structural changes (reduced exchange area, altered vascular structure) that we and others have previously shown in the FGR/MNR placenta which lead to deficits in placental function are mitigated by our repeated nanoparticle-mediated hIGF1 treatment. Sham-treated MNR placentas displayed disorganized microvasculature labyrinthine exchange areas with a reduction in placental capillary number and maternal blood space areas, and an increase in the volume of the placenta macrovasculature. Repeated nanoparticle-mediated hIGF1 treatment, however, resulted in an improved exchange area with normalized placental capillary number and maternal blood space area, and macrovasculature volume. This data demonstrates repeated nanoparticle-mediated hIGF1 delivery corrects aberrant placenta structure likely leading to improved gas exchange and transfer of nutrients to the fetus restoring fetal growth.

developmental biology↗

bioRxiv2025

Dynamics and fermentation patterns of stool microbiota on simple carbon sources in in vitro batch cultures reveal dysbiosis in Crohn's disease.

Crohns disease (CD)-associated dysbiosis is characterized by reduced microbial diversity, depletion of short-chain fatty acid (SCFA) producers, especially butyrate-forming taxa, and altered metabolic profiles. This study examined whether CD-related dysbiosis is reflected in the fermentation behavior of stool-derived microbial communities cultured in vitro on simple carbon substrates (glucose or acetate+lactate). Shotgun metagenomics and metabolomics revealed that CD-derived communities produced lower levels of butyrate (mainly via lactate and acetate), valerate, caproate, and propionate, and higher levels of ethanol and certain amino acids compared to healthy controls. These metabolic alterations aligned with compositional shifts, including a loss of beneficial commensals (e.g., Coprococcus catus, Ruminococcus torques, Eubacterium rectale, Fusicatenibacter saccharivorans, and Faecalibacterium prausnitzii) and an overrepresentation of CD-associated taxa, particularly Escherichia coli. Metabolic potential analysis revealed an enrichment of genes linked to ethanol and amino acid synthesis in CD-associated microbiotas, underscoring the metabolic adaptability of E. coli. Notably, acetate+lactate substrates supported the growth of healthy microbiota-associated bacteria, whereas glucose favored CD-associated taxa, highlighting disease-specific metabolic imbalances. These findings suggest that in vitro fermentation profiling may help distinguish CD-associated dysbiosis from a healthy microbiome and might support the development of microbiome-informed diagnostic or therapeutic approaches for CD. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=171 SRC="FIGDIR/small/656803v1_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@809890org.highwire.dtl.DTLVardef@a04b89org.highwire.dtl.DTLVardef@1bf39c0org.highwire.dtl.DTLVardef@1687974_HPS_FORMAT_FIGEXP M_FIG C_FIG A short abstract: CD-related dysbiosis alters stool microbial fermentation, reducing butyrate, propionate, valerate, caproate, and increasing ethanol/amino acids in vitro. Fermentation tests may help distinguish CD-associated patterns, suggesting potential for future microbiome-based diagnostics.

microbiology↗

bioRxiv2025

Real-Time Visualization of Calcium Phosphate Formation on Titanium Dioxide Nanoparticles Using Liquid Transmission Electron Microscopy

The integration of titanium dioxide (TiO2) with calcium phosphate (CaP)-based hydroxyapatite (HAP) is a promising strategy for enhancing the bioactivity of bone implants. However, a fundamental understanding of the interfacial reactions governing CaP mineralization on TiO2 remains limited due to lack of characterization techniques with sufficient spatial and temporal resolution in hydrated state. In this study, we combined in situ liquid TEM imaging and correlative ex situ TEM analyses to investigate the nucleation, aggregation, and crystallization of the CaP layer on TiO2 nanoparticle surfaces. Our findings reveal a three-step mineralization process: (1) initial aggregation of TiO2 nanoparticles in solution, (2) formation of an amorphous calcium phosphate-like (ACP-like) layer on the TiO2 surface, leading to an ACP-like coated TiO2 nanoparticle structure, and (3) progressive crystallization of ACP into HAP, forming a HAP-like coated TiO2 nanoparticle structure. Liquid-TEM imaging captured dynamic transformations, including nanoparticle aggregation, structural evolution, and phase transitions, providing unprecedented insights into the physicochemical interactions underlying mineralization. Additionally, we evaluated the effects of electron beam exposure on TiO2 nanoparticles, demonstrating that high electron flux densities can induce morphological instability. This study advances our understanding of CaP-TiO2 interfacial mineralization and offers valuable guidance for optimizing bioactive coatings to improve osseointegration and the long-term stability of bone implants.

bioengineering↗

bioRxiv2025

3D Focused Ion Beam Microscopy of Fossilized Albertosaurus sarcophagus reveals Nano to Microscale Structures

Osteohistological investigations of fossilized bone can reveal details about the specimens biological, geological and environmental conditions. Micro-to-nanoscale imaging provides insight into the structural organization of bone and can also reveal indicators of the fossilization process. We examined a petrographic thin section of the left fibula of a [~]71.5 million-year-old Albertosaurus sarcophagus (Canadian Museum of Nature [CMN] catalogue number FV 11315) using nanoscale scanning electron microscopy (SEM) and focused ion beam (FIB)-SEM tomographic imaging to study the arrangement of mineral and organic components of fossil bone in multidimensions. Here, we present evidence of permineralization in Haversian canals by energy dispersive X-ray spectroscopy. Nanoscale 3D FIB-SEM imaging revealed that the characteristic 67 nm banding periodicity of collagen fibrils was remarkably well preserved over 70M years, and 3D imaging allowed for the detection of collagen fibril bundles in parallel fibered and lamellar bone arrangements. A newly discovered structure in modern bone, the ellipsoidal mineral cluster, was tiled throughout the 3D space of fibrolamellar fossil bone. These observations, afforded by the high-resolution and site-specific nature of FIB-SEM, link key fossilized features with the micro-nanoscale structure of modern-day bone. This investigation highlights the persistence of bone formation and organization persisting for over millions of years.

paleontology↗

bioRxiv2025

Th1 cells express Tfh effector molecules and associate with B cells at the T-B borderfollowing viral infection

Antibodies protect the host from pathogens by neutralizing viruses, targeting pathogens for phagocytosis and complement deposition, and by activating innate immune cells. Most studies on the cellular mechanisms of antibody induction focus on the role of germinal centers (GCs) - areas within lymph nodes (LNs) and spleen where activated B cells undergo mutation and then selection by T follicular helper (Tfh) cells to produce high affinity antibodies. However, specific and long-lived antibodies can be produced in the absence of GCs and Tfh cells, sometimes referred to as "extrafollicular" (EF) responses. However, EF responses are typically assumed to be short-lived and low affinity. We characterized the CD4+ T cells present in wild type and Tfh cell-deficient mice in lung draining LNs following influenza A virus or SARS-CoV-2 infection to compare the nature of T cell help for activated B cells. We found that a population of helper Th1 cells remains in LNs seven days following viral infection and interacts with IgG2c+ B cells at the T-B border in both WT and Tfh-deficient mice. We propose that Th1 cells promote virus-specific antibody production in parallel with Tfh cells in the GC and that such a response is contiguous with the T-B border and therefore is not an EF response as classically defined.

immunology↗

bioRxiv2025

Prominent white matter related abnormalities associated with diverse molecular alterations in a mouse model of Col4a1 cerebral small vessel disease.

White matter abnormalities are a hallmark of cerebral small vessel disease (cSVD) and are closely linked to cognitive decline and dementia. However, despite their clinical importance, underlying mechanisms remain poorly understood. Collagen IV, encoded by genes COL4A1/COL4A2, is a major component of the basement membrane, a specialised extracellular matrix (ECM) structure. Mutations in these genes cause a genetic form of cSVD. We tested the hypothesis that ECM defects caused by a Col4a1 mutation lead to white matter pathology using an established mouse model of cSVD (Col4a1+/Svc). Behavioural testing with magnetic resonance diffusion tensor imaging, pathology and ultrastructural investigations of white matter were studied. The studies revealed that Col4a1+/Svc mice have cognitive impairments, reduced myelinating oligodendrocyte pools, axonal myelination defects, and altered white matter structural integrity. Proteomic analysis, of isolated white matter from Col4a1+/Svcmice, identified extensive changes to ECM composition and endoplasmic reticulum (ER) biology including ER stress induction. We also demonstrated that targeting protein folding to promote collagen secretion and reduce ER stress, increased myelinating oligodendrocytes and axon-glial integrity in Col4a1+/Svc mice. These data provide novel insight into the pathomolecular mechanisms of white matter abnormalities in cSVD and identify a modifiable pathway as a putative therapeutic target for cSVD.

neuroscience↗

bioRxiv2025

Temporal Dynamics of the Vaginal Microbiome and Host Immune Markers Before, During, and After Metronidazole Treatment for Bacterial Vaginosis

This study analyzed metagenomic and immune marker profiles of seven individuals before, during, and after a 7-day course of metronidazole treatment for bacterial vaginosis (BV). Treatment reduced BV-associated bacteria and immune marker levels, with distinct early (days 1-4) and late (days 5-7) phases. Post-treatment, variability in microbial and immune marker profiles demonstrated a rapid resurgence of certain BV associated bacteria, highlighting the need for additional strategies like probiotics to maintain a healthy vaginal microbiome. The study found significant host and microbial influences on immune response variance, with IP-10 and sEcad highly correlated with the vaginal microbiome. The findings identify optimal timing for administering live biotherapeutics to restore D-lactic acid-producing Lactobacillus species dominance and underscore the complexity of BV infection and treatment response among different people. ImportanceBacterial vaginosis (BV), a common condition associated with an increased risk of preterm birth and sexually transmitted infections among others, is characterized by a dysbiotic vaginal microbiome associated with dominance of a diverse assortment of anaerobic bacterial species. Metronidazole is the first-line treatment recommended by the CDC for BV when patients report symptoms. Despite treatment, BV recurrence is common. There is limited data regarding the effects of oral metronidazole on the vaginal microbiome starting at initiation of treatment as most studies have compared measurements taken before and after treatment completion. This study utilized metagenomic sequencing, pan-bacterial qPCR, and immune marker measurements to analyze the longitudinal dynamics of the vaginal microbiome and host immune response before, during and after metronidazole treatment.

microbiology↗

bioRxiv2025

Placenta hIGF1 nanoparticle treatment in guinea pigs mitigates fetal sex dependent FGR-associated effects on kidney structure and blood pressure-related signaling pathways

Fetal development in an adverse in utero environment significantly increases the risk of hypertension and cardiovascular disease. The kidneys play a pivotal role in the regulation of blood pressure and cardiovascular function, and perturbations in kidney structure and molecular profile are often demonstrated in offspring born fetal growth restricted (FGR). The aim of this study was to determine whether improving the in utero fetal growth environment with a placental nanoparticle gene therapy would ameliorate FGR-associated dysregulation of fetal kidney development. Using the guinea pig maternal nutrient restriction (MNR) model, we improved placenta efficiency and fetal weight following three placental administrations of a non-viral polymer-based nanoparticle gene therapy from mid-pregnancy (gestational day 35) until gestational day 52. The nanoparticle gene therapy transiently increased expression of human insulin-like growth factor 1 (hIGF1) in placenta trophoblast. Fetal kidney tissue was collected near-term at gestational day 60. Differences in kidney structure, glomeruli size and gene expression of extracellular matrix (ECM) remodeling and blood pressure regulation-related factors were demonstrated in sham-treated FGR fetuses but not observed in FGR fetuses who received placental hIGF1 nanoparticle treatment. We speculate that mitigating the FGR-associated changes in kidney architecture and molecular profiles might confer protection against increased susceptibility to aberrant kidney physiology in later-life. Overall, this work opens avenues for future research to assess the long-term impact of the placental hIGF1 nanoparticle gene therapy on cardiovascular function in offspring.

physiology↗

bioRxiv2025

Multiregional blood-brain barrier phenotyping identifies the prefrontal cortex as the most vulnerable region to ageing in mice

Age-associated vascular alterations make the brain more vulnerable to neuropathologies. Research in humans and rodents have demonstrated structural, molecular, and functional alterations of the aged brain vasculature that suggest blood-brain barrier (BBB) dysfunction. However, these studies focused on particular features of the BBB and specific brain regions. Thus, it remains unclear if and which BBB age-associated phenotypes are conserved across brain areas. Moreover, there is very limited information about how BBB dysfunction and cell-specific phenotypes relate to each other. In this manuscript, we use immunofluorescence, transmission electron microscopy (TEM), and permeability assays to assess how age-associated BBB molecular, structural, and functional phenotypes correlate between the BBB cell types at three brain regions (prefrontal cortex, hippocampus, and corpus callosum) during mouse early ageing. We discovered that at 18-20 months of age, the mouse prefrontal cortex BBB is the most affected region, with alterations in brain endothelial cell protein expression, BBB permeability, basement membrane thickness, and astrocyte endfoot size when compared to young mice. Here, we deliver a detailed multicellular characterisation of region-dependent BBB changes at early stages of ageing. Our data paves the way for future studies to investigate how region-specific BBB dysfunction may contribute to disease-associated regional vulnerability.

neuroscience↗

bioRxiv2025

Complementary Volume Electron Microscopy-based approaches reveal ultrastructural changes in germline intercellular bridges of D. melanogaster

Intercellular bridges are essential to connect developing germline cells. The Drosophila melanogaster egg chamber is a powerful model system to study germline intercellular bridges, or ring canals (RCs). RCs connect the developing oocyte to supporting nurse cells, and defects in their stability or growth lead to infertility. Despite their importance, it has been technically difficult to use electron microscopy-based approaches to monitor changes in RC structure during oogenesis. Here, we describe the application of a complementary set of volume EM-based approaches to visualize ultrastructural changes in the germline RCs. The combination of array tomography (AT) and focused ion beam (FIB) scanning electron microscopy (SEM) has allowed us to gain insight into previously unappreciated aspects of RC structure. We were able to quantify differences in RC size and thickness within and between germ cell clusters at different developmental stages. Within a cluster, RC size correlates with lineage; the largest RCs were formed during the first division, and the smallest RCs were formed during the fourth mitotic division. We observed the formation of membrane interdigitations in the vicinity of RCs much earlier than previously reported, and reconstruction of a RC from a mid-stage EC provided insight into the 3D orientation of these extensive cell-cell contacts. Our imaging also revealed a novel membrane structure that appeared to line the interior of the RC lumen. Although the focus was on ultrastructural changes in the germline RCs, our dataset contains valuable details of additional cell types and structures, including the fusome, the germline stem cells and their niche, and the migrating border cells. This imaging framework could be applied to other tissues or samples that face similar technical challenges, where the small structure of interest is located within a large sample volume.

developmental biology↗

bioRxiv2025

Optimized vectors for genetic engineering of Aureobasidium pullulans

Aureobasidium pullulans is a polyextremotolerant black yeast that exhibits impressive morphological plasticity. Consequently, it shows promise as a model system for investigating mechanisms of cell adaptation to different environments and the regulation of cell shape. Here, we build upon the current toolkit for working with A. pullulans and design and test 25 vectors with seven different codon-optimized fluorophores and three selection cassettes. This includes vectors that allow for dual expression of GFP and mCherry tagged proteins at the URA3 locus and vectors that enable homology-based deletion or C-terminal tagging of endogenous genes without the need for cloning. This versatile vector series for working with A. pullulans will enable a broad range of experiments in this emerging model system. SUMMARYAn optimized plasmid toolkit for genetic engineering of the emerging model fungus, A. pullulans.

cell biology↗

bioRxiv2025

Placental Nutrient Transport and Signaling in a Guinea Pig Model of Fetal Growth Restriction with Repeated Placental Nanoparticle-mediated IGF1 Treatment

Roughly 10% of all pregnancies are affected by fetal growth restriction (FGR). The primary etiology of FGR is placental insufficiency: the placenta not providing the appropriate amount of nutrients and oxygen to the fetus. There is currently no treatment for FGR or placental insufficiency. Because of the placentas pivotal role in FGR and supplying nutrients to the fetus, it offers an excellent target for therapeutic intervention. Using a guinea pig maternal nutrient restriction model and a repeated placental nanoparticle-mediated IGF1 treatment, placental IGF1 signaling and nutrient transport pathways were characterized to understand changes with FGR and treatment. This study elucidates the signaling mechanisms in which repeated placental nanoparticle-mediated IGF1 treatment leads to correct fetal growth. Overall, this study resulted in sex-specific kinase signaling and nutrient transporter changes within the placenta in both FGR and treatment groups. Combined with our previous studies using this treatment, we demonstrate the basic molecular signaling of this treatment and recapitulate the plausibility of this therapy for future human translation.

molecular biology↗

bioRxiv2025

Common symbiotic signalling pathway not essential for formation of functional mutualisms with endophytic fungi

Most plants form mutualistic symbioses with soil fungi, including arbuscular mycorrhizal (AM) fungi. These fungi usually transfer soil nutrients to plants and assimilate carbon from host plant photosynthesis. Recently, Mucoromycotina fine root endophytes (MFRE) were identified as nutritionally mutualistic and widespread fungal symbionts of plants, establishing MFRE as a new class of mycorrhizal fungi. However, the regulatory mechanisms for MFRE symbioses are completely unknown. Other symbionts, like AM fungi, use the Common Symbiotic Signalling Pathway (CSSP) to establish symbiosis. To explore whether MFRE interactions also involve this pathway, we cultured MFRE with CSSP mutants of Medicago truncatula which show impaired AM symbioses and tracked carbon and nutrient transfers using isotope tracers. Results show no differences in root colonization or nutrient exchange, suggesting MFRE symbioses are regulated by different molecular mechanisms. This finding highlights the unique nature of MFRE symbiosis, broadening our understanding of diverse fungal symbioses and their evolutionary significance.

microbiology↗