Biology subjects

Ben Zeev, B.

Publications and source records attributed to Ben Zeev, B..

3 recordsLinked to original sources

bioRxiv2026

Cross-species analysis of GNB1 I80T encephalopathy: conserved developmental, epileptic and neuronal transcriptome signatures

GNB1 encephalopathy (GNB1E) is a rare neurodevelopmental disorder caused by mutations in GNB1 gene encoding the G protein subunit G{beta}1. Mechanisms linking these variants to neurological dysfunction remain unclear. We investigated the prevalent p.Ile80Thr (I80T) variant using combined clinical, cellular, and in vivo approaches. Longitudinal evaluation of a GNB1E patient revealed developmental delay, progressive peripheral spasticity, and epilepsy with Spike-Wave Activation in Sleep. Heterozygous knock-in Gnb1I80T/+ mice exhibited disease-relevant phenotypes, including impaired early development, mild adult motor and cognitive deficits and epileptiform cortical spike-and-wave discharges. Transcriptomic analysis identified 323 genes concordantly dysregulated in mouse cortex and cortical human neuronal cultures from patient-derived induced pluripotent cells. This gene set was enriched for ion-channel function, epilepsy-associated genes, and Gs/adenylyl cyclase signaling pathway. Our integrated analysis establishes the first cross-species model for GNB1E, suggests common neurological mechanisms and molecular pathways linked to GNB1E, and provides a framework for mechanistic and therapeutic studies. TeaserConserved human/mouse neurological and transcriptomic signatures in GNB1 encephalopathy.

physiology↗

bioRxiv2025

Disentangling the stomatal response to transpiration and relative humidity

Stomatal responses to atmospheric conditions are critical for balancing plant CO2 gain with water loss. Yet, the question of whether stomata respond directly to humidity or to the rate of water loss (transpiration) remains unresolved due to the tight coupling between these variables. To decouple them, we manipulated water vapor diffusivity using Helox (21% O2, 79% He), where vapor diffuses 2.33 times faster than in air, and Argox (21% O2, 79% Ar), where it diffuses 0.75 times slower. This allows control of VPD and transpiration independent of one another while maintaining a constant leaf temperature. We investigated the stomatal conductance (gsw) responses to air and Helox in several plant species, including Solanum lycopersicum, Vitis vinifera, and the fern Nephrolepis exaltata. In addition, we tested the Commelina communis, with coupled gas exchange and real-time imaging of stomatal aperture in intact leaves. In all angiosperms tested, we observed that stomatal closing was triggered exclusively by reductions in RH rather than by transpiration increases. When transpiration increased, but relative humidity remained constant, we detected an increase in gsw without a following decrease in the experimental time span. Exposure to Argox without altering RH reduced transpiration, likely enabling restoration of epidermal turgor and inducing passive mechanical closure. However, the rate of stomatal closure under reduced RH was 2.35 times faster than that observed under Argox, suggesting that passive turgor-driven responses cannot fully explain the kinetics or extent of closure under dry air. This work provides direct experimental evidence for humidity-driven stomatal closure.

plant biology↗

bioRxiv2023

PRDM16 co-operates with LHX2 to shape the human brain

PRDM16 is a dynamic transcriptional regulator of various stem cell niches, including adipocytic, hematopoietic, cardiac progenitors, and neural stem cells. PRDM16 has been suggested to contribute to 1p36 deletion syndrome, one of the most prevalent subtelomeric microdeletion syndromes. We report a patient with a de novo nonsense mutation in the PRDM16 coding sequence, accompanied by lissencephaly and microcephaly features. Human stem cells were genetically modified to mimic this mutation, generating cortical organoids that exhibited altered cell cycle dynamics. RNA sequencing of cortical organoids at day 32 unveiled changes in cell adhesion and WNT-signaling pathways. ChIP-seq of PRDM16 identified binding sites in postmortem human fetal cortex, indicating the conservation of PRDM16 binding to developmental genes in mice and humans, potentially at enhancer sites. A shared motif between PRDM16 and LHX2 was identified and further examined through comparison with LHX2 ChIP-seq data from mice. These results suggested a collaborative partnership between PRDM16 and LHX2 in regulating a common set of genes and pathways in cortical radial glia cells, possibly via their synergistic involvement in cortical development.

developmental biology↗