Biology subjects

Scala, F.

Publications and source records attributed to Scala, F..

6 recordsLinked to original sources

bioRxiv2026

High-Throughput, automated assay for detection of colonization by Candida auris

Candida auris is an emerging multidrug-resistant fungal pathogen associated with healthcare-associated outbreaks, persistent colonization, and invasive infections. Increasing demand for surveillance has created a need for high-throughput methods capable of supporting large-scale screening programs. We developed and validated an automated laboratory-developed real-time PCR assay for detection of C. auris colonization on the Hologic Panther Fusion(R) open-access platform and compared its performance with the existing BD MAX assay. Analytical performance was evaluated by assessing limit of detection, accuracy, precision, specificity, inclusivity, reproducibility, and reagent and specimen stability. The Panther Fusion(R) assay demonstrated a limit of detection of approximately 18 CFU/reaction and showed 97% overall agreement with the BD MAX assay. Positive and negative percent agreement were 94% and 100%, respectively, with excellent agreement between methods ({kappa} = 0.94). No cross-reactivity was observed with non-C. auris organisms, all five major C. auris clades were detected, and assay performance remained stable across operators, reagent and specimen storage conditions. Following implementation, 26,838 clinical specimens were tested on the Panther Fusion(R) platform. Retrospective analysis demonstrated lower equivocal (0.28%) and indeterminate (0.09%) rates than those observed on the ABI and BD MAX platforms. Among PCR-positive specimens that underwent culture, the Panther Fusion(R) assay demonstrated 87.24% culture agreement. Because retrospective data were collected during different testing periods and patient populations, comparisons between platforms were not used to assess relative assay sensitivity or specificity. Implementation of the Panther Fusion(R) assay increased surveillance testing capacity from approximately 88 to 500 specimens per shift while maintaining robust analytical performance.

microbiology↗

bioRxiv2023

Combined statistical-mechanistic modeling links ionchannel genes to physiology of cortical neuron types

Neural cell types have classically been characterized by their anatomy and electrophysiology. More recently, single-cell transcriptomics has enabled an increasingly fine genetically defined taxonomy of cortical cell types, but the link between the gene expression of individual cell types and their physiological and anatomical properties remains poorly understood. Here, we develop a hybrid modeling approach to bridge this gap. Our approach combines statistical and mechanistic models to predict cells electrophysiological activity from their gene expression pattern. To this end, we fit biophysical Hodgkin-Huxley-based models for a wide variety of cortical cell types using simulation-based inference, while overcoming the challenge posed by the mismatch between the mathematical model and the data. Using multimodal Patch-seq data, we link the estimated model parameters to gene expression using an interpretable sparse linear regression model. Our approach recovers specific ion channel gene expressions as predictive of biophysical model parameters including ion channel densities, directly implicating their mechanistic role in determining neural firing.

neuroscience↗

bioRxiv2020

Distinct organization of two cortico-cortical feedback pathways

Neocortical feedback is critical for processes like attention, prediction, and learning. A mechanistic understanding of its function requires deciphering its cell-type wiring logic. Recent studies revealed a disinhibitory circuit between motor and sensory areas in mice, where feedback preferentially targets vasointestinal peptide-expressing interneurons, in addition to pyramidal cells. It is unknown whether this circuit motif is a general cortico-cortical feedback organizing principle. Combining multiple simultaneous whole-cell recordings with optogenetics we found that in contrast to this wiring rule, feedback between the hierarchically organized visual areas (lateral-medial to V1) preferentially activated somatostatin-expressing interneurons. Functionally, both feedback circuits temporally sharpened feed-forward excitation by eliciting a transient increase followed by a prolonged decrease in pyramidal firing rate under sustained feed-forward input. However, under feed-forward transient input, the motor-sensory feedback facilitated pyramidal cell bursting while visual feedback increased spike time precision. Our findings argue for multiple feedback motifs implementing different dynamic non-linear operations.

neuroscience↗

bioRxiv2020

Phenotypic variation within and across transcriptomic cell types in mouse motor cortex

Cortical neurons exhibit astounding diversity in gene expression as well as in morphological and electrophysiological properties. Most existing neural taxonomies are based on either transcriptomic or morpho-electric criteria, as it has been technically challenging to study both aspects of neuronal diversity in the same set of cells. Here we used Patch-seq to combine patch-clamp recording, biocytin staining, and single-cell RNA sequencing of over 1300 neurons in adult mouse motor cortex, providing a comprehensive morpho-electric annotation of almost all transcriptomically defined neural cell types. We found that, although broad families of transcriptomic types (Vip, Pvalb, Sst, etc.) had distinct and essentially non-overlapping morpho-electric phenotypes, individual transcriptomic types within the same family were not well-separated in the morpho-electric space. Instead, there was a continuum of variability in morphology and electrophysiology, with neighbouring transcriptomic cell types showing similar morpho-electric features, often without clear boundaries between them. Our results suggest that neural types in the neocortex do not always form discrete entities. Instead, neurons follow a hierarchy consisting of distinct non-overlapping branches at the level of families, but can form continuous and correlated transcriptomic and morpho-electrical landscapes within families.

neuroscience↗

bioRxiv2019

Cell type composition and circuit organization of neocortical radial clones

SummaryExcitatory neurons arising from a common progenitor establish radially-oriented clonal units in the neocortex which have been proposed to serve as elementary information processing modules. To characterize the cell types and circuit diagram within these clonal units, we performed single-cell RNA-sequencing and multi-cell patch clamp recordings of neurons derived from Nestin-positive progenitors. We found that radial clones do not appear to be fate-restricted, but instead individual clones are composed of a random sampling of the transcriptomic cell types present in a particular cortical area. The effect of lineage on synaptic connectivity depends on the type of connection tested: pairs of clonally related neurons were more likely to be connected vertically, across cortical layers, but not laterally within the same layer, compared to unrelated pairs. We propose that integration of vertical input from related neurons with lateral input from unrelated neurons may represent a developmentally programmed motif for assembling neocortical circuits.

neuroscience↗

bioRxiv2018

Neocortical layer 4 in adult mouse differs in major cell types and circuit organization between primary sensory areas

Layer 4 (L4) of mammalian neocortex plays a crucial role in cortical information processing, yet a complete census of its cell types and connectivity remains elusive. Using whole-cell recordings with morphological recovery, we identified one major excitatory and seven inhibitory types of neurons in L4 of adult mouse visual cortex (V1). Nearly all excitatory neurons were pyramidal and almost all Somatostatin-positive (SOM+) neurons were Martinotti cells. In contrast, in somatosensory cortex (S1), excitatory cells were mostly stellate and SOM+ cells were non-Martinotti. These morphologically distinct SOM+ interneurons correspond to different transcriptomic cell types and are differentially integrated into the local circuit with only S1 cells receiving local excitatory input. Our results challenge the classical view of a canonical microcircuit repeated through the neocortex. Instead we propose that cell-type specific circuit motifs, such as the Martinotti/pyramidal pair, are optionally used across the cortex as building blocks to assemble cortical circuits.

neuroscience↗