Biology subjects

Filippi, C.

Publications and source records attributed to Filippi, C..

6 recordsLinked to original sources

bioRxiv2026

CICADA: A unified framework for NWB-based neurophysiological data analysis

Neurophysiology datasets are becoming increasingly complex, combining behavioral measurements with high-dimensional neuronal activity recordings coming from optical and/or electrophysiological measurements. The Neurodata Without Borders (NWB) standard has emerged in the community as the format of record. While standardized and widely used preprocessing tools generating NWB files have been developed, extensible frameworks for scientific analysis downstream of the NWB ecosystem are still under-represented. We present CICADA, a Python framework dedicated to analysis of neurophysiological data in the standardized NWB format. The toolbox is built as three hierarchically-organized packages: cicada-nwb (NWB access layer), cicada-analysis (plugin-based analysis engine and tool library), and cicada-gui (PyQt5 desktop application at the head of the pipeline). Beyond this architectural separation, CICADA is built around a central design principle: supporting a continuum from turnkey use to full modularity. Researchers can use the complete GUI-driven cicada-gui workflow without writing code, programmatically use existing analysis plugins from cicada-analysis, contribute to new analysis plugins, reuse utilities from cicada-tools, or build entirely custom pipelines on top of the cicada-nwb access layer alone. The same analysis plugin runs identically in interactive GUI and parameter-configured headless modes, enabling reproducible multi-session, multi-animal group analyses. We illustrate the versatility of CICADA with example analyses of behavioral, calcium imaging (two-photon and widefield) and extracellular electrophysiology datasets from rodent laboratories. CICADA is open source, actively maintained, and designed so that any laboratory can contribute at any level of the stack without modifying the core framework.

neuroscience↗

bioRxiv2026

Exploring the potential role of the TETRATRICOPEPTIDE THIOREDOXIN-LIKE gene family in nitrogen-fixing and water-restricted soybean plants

The TETRATRICOPEPTIDE THIOREDOXIN-LIKE (TTL) proteins are a plant-specific family proposed to function as peripheral membrane proteins that contribute to abiotic stress tolerance in Arabidopsis, likely by maintaining cell wall integrity through brassinosteroid signaling. Previously, we identified a TTL gene that was differentially regulated at the translational level in nitrogen-fixing soybean plants under water deficit (WD) conditions. This finding prompted the characterization of the soybean TTL gene family. Using the Glycine max v4.0 proteome, we identified ten TTL homologs (GmTTL1-GmTTL10), which are unevenly distributed across five chromosomes. Phylogenetic and structural analyses grouped these genes into three clades and revealed a highly conserved exon-intron organization. Likewise, GmTTL proteins display a conserved number and arrangement of TPR and TRXL motifs. To gain insights into their potential biological functions, we integrated co-expression and differential expression analyses. This approach identified a co-expression module enriched for translationally downregulated genes related to the Gene Ontology terms "cellular anatomical entity", "membrane", "cell periphery", "cell wall modification", "nitrate assimilation", and "cell wall organization or biogenesis". Protein-protein interaction network analysis of this specific subset of genes uncovered a novel GmTTL connection with two nitrate reductase enzymes in nitrogen-fixing plants subjected to WD, potentially linking the TTL gene family to new functions or roles. This study provides a framework for future functional studies of GmTTL proteins and their contribution to abiotic stress adaptation in soybean. Key MessageThis work presents the first functional characterization of TTLs proteins in legume species and highlights key processes that may link the TTL gene family to new functions or roles.

Plant Biology↗

bioRxiv2025

Distinct developmental trajectories of externally- and internally-generated hippocampal sequences and assemblies

The hippocampus generates cognitive maps through two distinct mechanisms: external representations anchored to environmental landmarks and internal sequences integrating self-referenced information. In adult CA1, these functions segregate radially, with deep cells processing external cues and superficial cells handling internal representations. This anatomical organization suggests that developmental processes constrain the formation of these functionally distinct circuits. However, the developmental timeline for the emergence of these two types of hippocampal representations remains unknown. Using longitudinal two-photon calcium imaging in head-fixed mice during the third postnatal week, we investigated when internal versus external hippocampal representations emerge. We recorded from deep and superficial CA1 layers while mice ran on treadmills that are bare or enriched with tactile cues, addressing the challenge of tracking cells across sessions. Internal sequences emerge during the mid-fourth postnatal week, following the development of cue-based representations. These sequences initially encode elapsed time before evolving to integrate run distance, arising after rest cell assemblies as spatial coding and functional connectivity networks stabilize. These findings identify the mid fourth postnatal week as a critical developmental milestone marking the establishment of a balanced integration between external landmark-based and internal self-referenced spatial representations. This transition period may constitute a vulnerable developmental window during which disruptions could predispose to disorders characterised by altered cognitive maps. HighlightsO_LIP24 is critical for CA1 development C_LIO_LICue-based representations stabilize by P24 C_LIO_LIInternal sequences emerge at P24, encoding run duration before distance C_LIO_LICell assemblies form before internal sequences C_LI

neuroscience↗

bioRxiv2022

Extrinsic control of the early postnatal CA1 hippocampal circuits

The adult CA1 region of the hippocampus produces coordinated neuronal dynamics with minimal reliance on its extrinsic inputs. In contrast, the neonatal CA1 is tightly linked to externally-generated sensorimotor activity but the circuit mechanisms underlying early synchronous activity in CA1 remain unclear. Here, using a combination of in vivo and ex vivo circuit mapping, calcium imaging and electrophysiological recordings in mouse pups, we show that early dynamics in the ventro-intermediate CA1 are under the mixed influence of entorhinal (EC) and thalamic (VMT) inputs. Both VMT and EC can drive internally-generated synchronous events ex vivo. However, movement-related population bursts detected in vivo are exclusively driven by the EC. These differential effects on synchrony reflect the different intrahippocampal targets of these inputs. Hence, cortical and subcortical pathways act differently on the neonatal CA1, implying distinct contributions to the development of the hippocampal microcircuit and related cognitive maps.

neuroscience↗

bioRxiv2021

Acetyl-CoA metabolism drives epigenome change and contributes to carcinogenesis risk in fatty liver disease

The rate of nonalcoholic fatty liver disease (NAFLD)-associated hepatocellular carcinoma (HCC) is increasing worldwide, but the steps in precancerous hepatocytes which lead to HCC driver mutations are not well understood. Here we provide evidence that metabolically-driven histone hyperacetylation in steatotic hepatocytes can increase DNA damage to initiate carcinogenesis. Genome-wide histone acetylation is increased in steatotic livers of rodents fed high fructose or high fat diet. In vitro, steatosis relaxes chromatin and increases DNA damage marker {gamma}H2AX, which is reversed by inhibiting acetyl-CoA production. Steatosis-associated acetylation and {gamma}H2AX are enriched at gene clusters in telomere-proximal regions which contain HCC tumor suppressors in hepatocytes and human fatty livers. Regions of metabolically-driven epigenetic change also have increased levels of DNA mutation in non-cancerous tissue from NAFLD patients. Finally, genome-scale network modelling indicates that redox balance is a key contributor to this mechanism. Thus abnormal histone hyperacetylation is a potential initiating event in HCC carcinogenesis.

cancer biology↗

bioRxiv2020

Functional spreading of hyperexcitability induced by human and synthetic intracellular Aβ oligomers

BackgroundIntracellular amyloid-beta oligomers (iA{beta}o) accumulation and neuronal hyperexcitability are two crucial events at early stages of Alzheimers disease (AD). However, to date, no mechanism linking them has been reported. MethodsHere, the effects of human AD brain-derived (h-iA{beta}o) and synthetic (iA{beta}o) peptides on synaptic currents and action potential (AP) firing were investigated in hippocampal neurons in vitro, ex vivo and in vivo. ResultsStarting from 500 pM, iA{beta}o rapidly increased the frequency of synaptic currents and higher concentrations potentiated the AMPA receptor-mediated current. Both effects were PKC-dependent. Parallel recordings of synaptic currents and nitric oxide (NO)-related fluorescence changes indicated that the increased frequency, related to pre-synaptic release, was dependent on a NO-mediated retrograde signaling. Moreover, increased synchronization in NO production was also observed in neurons neighboring those dialyzed with iA{beta}o, indicating that iA{beta}o can increase network excitability at a distance. Current-clamp recordings suggested that iA{beta}o increased neuronal excitability via AMPA-driven synaptic activity without altering membrane intrinsic properties. ConclusionThese results strongly indicate that iA{beta}o causes functional spreading of hyperexcitability through a synaptic-driven mechanism and offer an important neuropathological significance to intracellular species in the initial stages of AD, which include brain hyperexcitability and seizures.

neuroscience↗