Biology subjects

Ott, H.

Publications and source records attributed to Ott, H..

5 recordsLinked to original sources

bioRxiv2026

Simulating neural network criticality and resource dynamics with Rydberg gases

Efficient operation of neural networks has been linked to criticality in their underlying non-equilibrium excitation dynamics. However, obtaining experimental evidence of this conjecture remains challenging due to limited control and undersampling in biological systems. Here, we experimentally explore neural network criticality using an ultracold Rydberg gas as a highly controllable simulator. We highlight the similarity of the excitation spreading via Rydberg facilitation and the synaptic connection of spiking activity of neurons, giving rise to distinct absorbing and active phases. We systematically explore and resolve criticality criteria, including power-law scaling of excitation avalanches and the emergence of universal avalanche shape collapse. Crucially, we implement a controlled gain mechanism to compensate for atom loss, mimicking metabolic resource replenishment and stabilizing the system in a controlled non-equilibrium steady state. We find peak temporal correlations at the critical point and stochastic oscillations with dragon king avalanches in the active phase, consistent with predictions for systems orbiting criticality. Our work establishes facilitated Rydberg gases as a platform for investigating criticality, resource dynamics, and emergent oscillations in neural networks.

neuroscience↗

bioRxiv2025

Identification and characterization of a Fibrillin-1 derived matrikine for cardiac regeneration and repair

The development of regenerative strategies to repair the heart is of high importance. Our lab has shown that extracellular matrix derived from decellularized fetal myocardium promotes neonatal cardiomyocyte proliferation in vitro. The goal of this study was to identify specific peptide(s)/protein(s) in solubilized cardiac ECM responsible for this proliferative effect. We hypothesized that isolation and then treatment with one or more small synthetic peptide derived from this source could replicate the cellular response to whole solubilized ECM. Decellularized fetal and adult rat hearts were fractionated by molecular weight using SDS-PAGE and transferred to PVDF membranes. Analysis of cardiomyocytes cultured on the membranes revealed regions of enhanced cardiomyocyte proliferation. Subsequent isolation and proteomic analysis of the protein bands that that correlated with proliferative regions identified fibrillin-1 as the predominant ECM protein associated with these regions of cardiomyocyte proliferation. One region (residues 55-86) of fibrillin-1 was synthesized as a peptide and tested for a direct effect on cardiomyocyte proliferation. Compared to positive and negative controls, as well as scrambled and alkylated versions, this peptide led to 3-4 fold increase in cardiomyocyte proliferation. Analysis of the amino acid sequence demonstrated high homology with laent-TGF-{beta} binding proteins and subsequent experiments showed that the matrikine could also reduce TGF-{beta} induced activation of cardiac fibroblasts. These data suggest that individual peptides derived from soluble ECM could have utility as a novel therapeutic for cardiac tissue engineering and regeneration.

bioengineering↗

bioRxiv2025

Truncating RELA variants drive autoinflammation and autoimmunity by impairing the negative feedback control of NF-kB

The NF-{kappa}B signaling pathway coordinates inflammation, cell survival, and proliferation, while restraining excessive cell death to maintain immune homeostasis. Truncating mutations in RELA, encoding the NF-{kappa}B subunit p65, have been linked to autoinflammation and autoimmunity, but the underlying mechanisms remain incompletely defined. We investigated six patients from five unrelated families carrying novel heterozygous truncating RELA variants. Despite reduced p65 expression, patients exhibited a broad spectrum of inflammatory manifestations alongside elevated baseline and stimulus-induced pro-inflammatory cytokines. Functional analyses in patient-derived cells and mutant RELA knock-in models showed that upstream NF-{kappa}B signaling was intact, but induction of inhibitory regulators such as I{kappa}B and A20 was impaired. This defective feedback control shifted immune homeostasis toward amplified inflammatory responses that depended on the residual activity of the remaining functional RELA allele. Single-cell transcriptomics revealed distinct cell type-specific consequences: monocytes displayed constitutive type I interferon and NF-{kappa}B activation, B cells retained partial compensatory signaling, whereas T and NK cells exhibited transcriptional signatures of cell death pathways. Patient fibroblasts and mutant RELA knock-in cells further confirmed enhanced TNF-induced inflammatory gene expression and hypersensitivity to apoptosis and necroptosis. These findings establish RELA haploinsufficiency as a cause of systemic immune dysregulation, and link defective NF-{kappa}B feedback control to unchecked inflammation and inflammatory cell death. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=152 SRC="FIGDIR/small/687461v1_ufig1.gif" ALT="Figure 1"> View larger version (48K): org.highwire.dtl.DTLVardef@1f0bfe6org.highwire.dtl.DTLVardef@c6cb60org.highwire.dtl.DTLVardef@1522accorg.highwire.dtl.DTLVardef@177c724_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2024

MyVivarium: A cloud-based lab animal colony management application with near-realtime ambient sensing

Management of research-animal colonies is vital for lab productivity in preclinical research. Labs often rely on inefficient paper-based or spreadsheet-based methods to manage animal colonies. Dedicated software-based solutions are generally expensive and many lack remote access. Currently available open-source alternatives are difficult to implement and deploy. These solutions also do not have the capability to track ambient variables that affect colony well-being. We built MyVivarium, an open-source database management web application to address these gaps. MyVivarium can be easily deployed to the cloud and sustained for a cost comparable to starting and maintaining a lab website. Using MyVivarium, lab members can collaboratively track individual animals within a database. Physical identities of cages map onto the database using QR codes, enabling quick and easy record-keeping on mobile devices. Lab administrators can assign tasks to users with reminders for experiments or cage maintenance. Finally, we designed a low-cost system to sense ambient humidity, temperature, vivarium worker activity, and room illuminance. These data are then sent to MyVivarium in realtime providing information relevant to colony well-being. Taken together, MyVivarium is a novel, open-source, cloud-based application template that provides a low-cost, simple, and efficient way to digitally manage research-animal colonies.

bioinformatics↗

bioRxiv2023

A Novel Role for Phospholamban in the Thalamic Reticular Nucleus

The thalamic reticular nucleus (TRN) is a critical brain region that greatly influences vital neurobehavioral processes, including executive functioning and the generation of sleep rhythms. Recently, TRN dysfunction was suggested to underlie hyperactivity, attention deficits, and sleep disturbances observed across various devastating neurodevelopmental disorders, including autism, schizophrenia and attention-deficit/hyperactivity disorder (ADHD). Notably, a highly specialized sarco- endoplasmic reticulum calcium (Ca2+) ATPase 2 (SERCA2)-dependent Ca2+ signaling network operates in the dendrites of TRN neurons to regulate their high-frequency bursting activity. Phospholamban (PLN) is a prominent regulator of the SERCA2 with an established role in maintaining Ca2+ homeostasis in the heart; although the interaction of PLN with SERCA2 has been largely regarded as cardiac-specific, our findings challenge this view and suggest that the role of PLN extends beyond the cardiovascular system to impact brain function. Specifically, we found PLN to be expressed in the TRN neurons of the adult mouse brain and utilized global constitutive and innovative conditional genetic mouse models, in combination with 5-choice serial reaction time task (5-CSRTT) and electroencephalography (EEG)-based somnography to assess the role of PLN in regulating executive functioning and sleep, two complex behaviors that map onto thalamic reticular circuits. Overall, the results of the present study show that perturbed PLN function in the TRN results in aberrant thalamic reticular behavioral phenotypes in mice (i.e., hyperactivity, impulsivity and sleep deficits) and support a novel role for PLN as a critical regulator of the SERCA2 in the thalamic reticular neurocircuitry.

neuroscience↗