Biology subjects

Zinger, A.

Publications and source records attributed to Zinger, A..

5 recordsLinked to original sources

bioRxiv2025

Contribution of the Tobamovirus resistance gene Tm-1 to control of ToBRFV resistance in tomato

Tomato brown rugose fruit virus (ToBRFV) is a rapidly spreading pathogen that poses a significant threat to tomato production worldwide. We previously identified a locus on tomato chromosome 11 controlling tolerance to the virus. We further established that combining this locus with one that maps to the Tm-1 region on chromosome 2 confers resistance to the virus. Here we sought to determine whether, and how, the Tm-1 gene itself is involved in ToBRFV resistance. Overexpression of Tm-1 in a tolerant genotype significantly reduced viral accumulation, conferring resistance to ToBRFV. On the other hand, overexpression of Tm-1 in a susceptible genotype only delayed symptom appearance. Moreover, effective RNAi-silencing of Tm-1 in the resistant genotype yielded susceptible plants. These findings show that the Tm-1 gene interacts genetically with the locus controlling tolerance on chromosome 11 and that this interaction is critical for achieving effective resistance to ToBRFV. In addition, the symptomatic plants obtained following silencing of Tm-1 in the resistant genotype indicate that tolerance is also dependent on normal expression levels of the recessive tm-1 allele.

plant biology↗

bioRxiv2024

Exosomes can modulate the early hyperexcitability in cortical neurons with ASD-associated Shank3 mutation.

Extracellular vesicles (EVs) are lipid membrane-bound structures that mediate intercellular communication by transferring diverse cargoes, including RNA and proteins. Shank3, a synaptic scaffolding protein critical for synapse structure and function, is implicated in autism spectrum disorder (ASD) and Phelan-McDermid Syndrome (PMS). Early hyperexcitability in cortical neurons is a recognized endophenotype in ASD. Here, we investigated EV-mediated effects in the context of Shank3 deficiency using human iPSC-derived cortical neurons and Shank3B-/- mice. Switching EVs between Shank3 mutant and control neurons revealed that Shank3 mutant-derived EVs transferred the hyperexcitability and accelerated maturation phenotypes to control neurons. This was driven by enriched synaptic proteins (e.g., ACTB, CFL1, AGRN, CLSTN1) in Shank3 mutant-derived EVs as confirmed by proteomic analysis. Conversely, control EVs failed to rescue mutant phenotypes consistent with their lower enrichment for synaptic proteins and related pathways. Further, EVs from mesenchymal stem cells (MSCs) and healthy donor iPSCs, containing synaptic modulators such as complement proteins (C1R, C1S), plasticity-related proteins (MDK, IGFBP3), and homeostatic regulators (FGF2, SFRP1), rescued the hyperexcitability and normalized the maturation in Shank3 mutant neurons. Moreover, intranasal administration of iPSC-derived EVs in Shank3B-/- mice significantly ameliorated ASD-like behavioral deficits, underscoring their therapeutic potential. Together, these findings reveal a novel EV-mediated mechanism for modulating dysregulated excitability and synaptic maturation, addressing a critical unmet need in ASD and related neurodevelopmental disorders treatment.

neuroscience↗

bioRxiv2023

Sex-dependent improvement in traumatic brain injury outcomes after liposomal delivery of dexamethasone in mice.

Traumatic Brain Injury (TBI) can have long-lasting physical, emotional, and cognitive consequences due to the neurodegeneration caused by its robust inflammatory response. Despite advances in rehabilitation care, effective neuroprotective treatments for TBI patients are lacking. Furthermore, current drug delivery methods for TBI treatment are inefficient in targeting inflamed brain areas. To address this issue, we have developed a liposomal nanocarrier (Lipo) encapsulating dexamethasone (Dex), an agonist for the glucocorticoid receptor utilized to alleviate inflammation and swelling in various conditions. In vitro studies show that Lipo-Dex were well tolerated in human and murine neural cells. Lipo-Dex showed significant suppression of inflammatory cytokines, IL-6 and TNF-, release after induction of neural inflammation with lipopolysaccharide. Further, the Lipo-Dex were administered to young adult male and female C57BL/6 mice immediately after a controlled cortical impact injury. Our findings demonstrate that Lipo-Dex can selectively target the injured brain, thereby reducing lesion volume, cell death, astrogliosis, the release of proinflammatory cytokines, and microglial activation compared to Lipo-treated mice in a sex-dependent manner, showing a major impact only in male mice. This highlights the importance of considering sex as a crucial variable in developing and evaluating new nano-therapies for brain injury. These results suggest that Lipo-Dex administration may effectively treat acute TBI.

neuroscience↗

bioRxiv2020

Chemotherapeutic Nanoparticles Accumulate in the Female Reproductive System during Ovulation Affecting Fertility and Anticancer Activity

Throughout the female menstrual cycle, physiological changes occur that affect the biodistribution of nanoparticles within the reproductive system. This can have positive or negative effects. We demonstrate a 2-fold increase in nanoparticle accumulation in the ovaries during female mouse ovulation compared to the non-ovulatory stage following intravenous administration. Accumulation in the reproductive system is favored by nanoparticles smaller than 100 nm. Chemotherapeutic nanoparticles administered during ovulation increased ovarian toxicity and decreased short-term and long-term fertility when compared to the free drug. Breast cancer treated with nanomedicines during ovulation results in higher drug accumulation in the reproductive system rather than at the site of the tumor, reducing treatment efficacy. Conversely, ovarian cancer treatment was improved by enhanced nanoparticle accumulation in the ovaries during ovulation. Our findings suggest that the menstrual cycle should be considered when designing and implementing nanotherapeutics for females.

bioengineering↗

bioRxiv2020

Skin protective effects of RM191A, a novel superoxide dismutase mimetic

Superoxide dismutase (SOD) is known to be protective against oxidative stress-mediated skin dysfunction. Here we explore the potential therapeutic activities of RM191A, a novel SOD mimetic, on skin. RM191A is a water soluble, dimeric copper (Cu2+-Cu3+)-centred polyglycine coordination complex. It displays 10-fold higher superoxide quenching activity compared to SOD as well as significant anti-inflammatory activity through beneficial modulation of several significant inflammatory pathways in cells. We tested the therapeutic potential of RM191A in a topical gel using a human skin explant model and observed that it significantly inhibits UV-induced DNA damage in the epidermis and dermis, including cyclobutane pyrimidine dimers (CPD), 8-oxo-guanine (8-oxoG) and 8-nitroguanine (8NGO). RM191A topical gel is found to be safe and non-toxic in mice following month-long daily dosing at 0.19 mL/kg body weight. Moreover, it significantly accelerates excisional wound healing, and reduces 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin inflammation in mice. HighlightsO_LISuperoxide dismutase mimetic RM191A is a highly stable copper (Cu2+-Cu3+)-polyglycine coordination complex C_LIO_LIRM191A exhibits potent antioxidant (10-fold more than that of superoxide dismutase) properties in vitro C_LIO_LIRM191A exhibits potent anti-inflammatory properties in vitro and in vivo C_LIO_LIRM191A protects human skin explants against UV-induced oxidative stress and DNA damage C_LIO_LIRM191A is non-toxic and readily bioavailable in mice C_LIO_LIRM191A attenuates TPA-induced skin inflammation and improves wound healing in mice C_LI

physiology↗