Biology subjects

Cruz, C.

Publications and source records attributed to Cruz, C..

5 recordsLinked to original sources

bioRxiv2025

In Utero Exposure to Anti-Caspr2 Antibody Disrupts Parvalbumin Interneuron Function in the Hippocampus

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by deficits in communication and social interaction and may stem from an imbalance between excitatory and inhibitory (E/I) signaling in neural circuits. Parvalbumin-expressing (PV+) interneurons are crucial for maintaining E/I balance and regulating network oscillations. Alterations in the number of PV+ interneurons or reductions in PV expression have been observed in both the postmortem brains of individuals with ASD and in animal models, including those induced by in utero exposure to maternal brain-reactive antibodies. In this study, we investigate the impact of in utero exposure to maternal anti-Caspr2 IgG on PV+ interneuron development and function in the hippocampus. Our results demonstrate a selective reduction in PV+ interneurons and perisomatic inhibitory synapses in the hippocampal CA1 region of juvenile and adult male offspring exposed in utero to anti-Caspr2 antibodies compared to controls. Additionally, local field potential (LFP) recordings from these mice show increased gamma power and altered neuronal firing patterns during social interactions, indicating functional impairments in inhibitory circuitry. These findings highlight the consequences of exposure to maternal anti-Caspr2 antibodies on PV+ interneuron development and function, providing insights into the neurobiological mechanisms underlying ASD associated behavioral phenotypes.

neuroscience↗

bioRxiv2025

The FANCD2-FANCI heterodimer coordinates chromatin openness and cell cycle progression throughout DNA double-strand break repair.

The FANCD2-FANCI heterodimer contributes to DNA repair at interstrand crosslinks and sites of replication stress. This complex has been physically and mechanistically linked to double-strand break (DSB) repair, but its role in that process remains undefined. Here we show that the FANCD2-FANCI heterodimer dynamically interacts with open chromatin regions, including transient, DSB-induced open chromatin, where it can be stabilized by co-activation by the DNA repair kinase ATM and the Fanconi anemia core ubiquitin ligase. The loaded FANCD2-FANCI heterodimer stabilizes open chromatin and promotes resection and loading of RPA through increased association of BRCA1 and BLM. Chromatin-loaded FANCD2-FANCI has a second distinct function promoting a G2 arrest that is dependent on the ATR-CHK1-WEE1 axis. Our results support a two-step genome surveillance model in which FANCD2-FANCI monitors open chromatin sites and is stably loaded to coordinate DNA repair activities in response to signaling from a DNA repair kinase.

cell biology↗

bioRxiv2024

Protecting Allogeneic Pancreatic Islet Grafts by Engineered Veto

In todays clinical practice, general immune suppression regimens are used to prevent transplant rejection. Though highly effective, they impair a patients protection against infectious challenges. Strategies are being sought that prevent graft rejection without inhibiting beneficial immune functions. One such approach is based on the classical veto effect that employs donor-derived CD8+ T cells to inhibit cellular immune responses. Yet, allogeneic grafts may only be partially protected by classical veto as CD8+ T cells may fail to remove organ-specific alloreactive T cells. To induce transplant specific immune unresponsiveness, if not tolerance, it may be necessary to endow grafted tissues with veto. Adenoviral vectors were designed that expressed the CD8 -chain as transgene and thus conferred the immune inhibitory veto function to cells of grafted tissues. In the present model, adenoviral vector vectors protected transduced allogeneic pancreatic islets from rejection in fully immune competent recipients. These studies demonstrated that a tissue-engineering approached could be used to create universally acceptable transplants.

immunology↗

bioRxiv2023

Enhancing gene set analysis in embedding spaces: a novel best-match approach

AO_SCPLOWBSTRACTC_SCPLOWEmbedding methods have emerged as a valuable class of approaches for distilling essential information from complex high-dimensional data into more accessible lower-dimensional spaces. Applications of embedding methods to biological data have demonstrated that gene embeddings can effectively capture physical, structural, and functional relationships between genes. However, this utility has been primarily realized by using gene embeddings for downstream machine learning tasks. Much less has been done to examine the embeddings directly, especially analyses of gene sets in embedding spaces. Here, we propose ANDES, a novel best-match approach that can be used with existing gene embeddings to compare gene sets while reconciling gene set diversity. This intuitive method has important downstream implications for improving the utility of embedding spaces for various tasks. Specifically, we show how ANDES, when applied to different gene embeddings encoding protein-protein interactions, can be used as a novel overrepresentation-based and rank-based gene set enrichment analysis method that achieves state-of-the-art performance. Additionally, ANDES can use multi-organism joint gene embeddings to facilitate functional knowledge transfer across organisms, allowing for phenotype mapping across model systems. Our flexible, straightforward best-match methodology can be extended to other embedding spaces with diverse community structures between set elements.

bioinformatics↗

bioRxiv2017

Tri-methylation of Histone H3 Lysine 4 Facilitates Gene Expression in Ageing Cells

Transcription of protein coding genes is accompanied by recruitment of COMPASS to promoter-proximal chromatin, which deposits di- and tri-methylation on histone H3 lysine 4 (H3K4) to form H3K4me2 and H3K4me3. Here we determine the importance of COMPASS in maintaining gene expression across lifespan in budding yeast. We find that COMPASS mutations dramatically reduce replicative lifespan and cause widespread gene expression defects. Known repressive functions of H3K4me2 are progressively lost with age, while hundreds of genes become dependent on H3K4me3 for full expression. Induction of these H3K4me3 dependent genes is also impacted in young cells lacking COMPASS components including the H3K4me3-specific factor Spp1. Remarkably, the genome-wide occurrence of H3K4me3 is progressively reduced with age despite widespread transcriptional induction, minimising the normal positive correlation between promoter H3K4me3 and gene expression. Our results provide clear evidence that H3K4me3 is required to attain normal expression levels of many genes across organismal lifespan.

genetics↗