Biology subjects

Campana, M.

Publications and source records attributed to Campana, M..

5 recordsLinked to original sources

bioRxiv2025

Contralateral Prefrontal and Network Engagement during Left DLPFC 10 Hz rTMS: An Interleaved TMS-fMRI Study in Healthy Adults

BackgroundHigh-frequency repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) serves as an effective treatment for major depression and other psychiatric disorders. Despite its growing clinical application, the neural mechanisms by which prefrontal rTMS exerts its therapeutic effects remain incompletely understood. To address this gap, we investigated the immediate blood-oxygen-level-dependent (BOLD) activity during 600 stimuli of left DLPFC 10 Hz rTMS in healthy individuals using interleaved TMS-fMRI. MethodsIn a crossover design, 17 healthy subjects received 10 Hz rTMS (60 trains with 9-second intertrain intervals) over the left DLPFC at 40% and 80% of their resting motor threshold (rMT) inside the MR scanner. Results10 Hz rTMS over the left DLPFC elicited BOLD responses in prefrontal regions, cingulate cortex, insula, striatum, thalamus, as well as auditory and somatosensory areas. Notably, our findings revealed that 10 Hz rTMS effects were lateralized towards the contralateral (right) DLPFC. Dose-response effects (40% vs. 80% rTMS) were exclusively observed in contralateral subcortical regions, whereas dose-responses within the DLPFC showed substantial inter-individual variability. ConclusionsThe 10 Hz rTMS protocol used in this study induced distinct target engagement and propagation patterns in the prefrontal cortex. These patterns differ from our previous interleaved TMS-fMRI findings using 600 stimuli of left DLPFC intermittent theta burst stimulation (iTBS) at the same intensities. Thus, interleaved TMS-fMRI emerges as a valuable method for comparing clinical prefrontal rTMS protocols regarding their immediate effect on brain circuits in order to differentiate their action mechanisms and to potentially inform clinical applications.

neuroscience↗

bioRxiv2024

Next-generation snow leopard population assessment tool: multiplex-PCR SNP panel for individual identification from feces

Snow leopards, Panthera uncia, are under threat from numerous pressures and are the focus of a great deal of conservation efforts. However, their elusive nature makes it difficult to estimate population sizes. Current methods used to monitor local population sizes include visually identifying individuals from camera trap photos and genetically identifying individuals from fecal samples using microsatellite loci. Here, we present a new method for identifying snow leopard individuals from fecal samples using a multiplex PCR single nucleotide polymorphism (SNP) panel method. The SNP panel we present consists of 144 SNPs and utilizes next-generation sequencing technology, making it cheaper and easier than current microsatellite methods. We validate our SNP panel with paired tissue and fecal samples from zoo individuals, showing a minimum of 96.7% accuracy in allele calls per run. We then generate SNP data from 235 field-collected fecal samples from across Pakistan to show that the panel can reliably identify individuals from low-quality fecal samples of unknown age and is robust to contamination. We also show that our SNP panel has the capability to identify first-order relatives and provides insights into the geographic origin of samples. This SNP panel will empower the snow leopard research community in their efforts to assess local and global snow leopard population sizes. More broadly, we present a method for developing a SNP panel that utilizes open source software for SNP selection and primer design, Illumina sequencing technology, and a streamlined lab and bioinformatics protocol which can be used to create similar SNP panels for any species of interest for which adequate genomic reference data is available.

genetics↗

bioRxiv2024

Parameterizing Pantherinae: de novo mutation rate estimates from Panthera and Neofelis pedigrees

Estimates of de novo mutation rates are essential for phylogenetic and demographic analyses, but their inference has previously been impeded by high error rates in sequence data and uncertainty in the fossil record. Here, we directly estimate de novo germline mutation rates for all extant members of Panthera, as well as the closely related outgroup Neofelis nebulosa, using pedigrees. We use a previously validated pipeline (RatesTools) to calculate mutation rate for each species and subsequently explore the impacts of the novel rates on historic effective population size estimates in each of these charismatic felids of conservation concern. Importantly, we find that the choice of reference genome, the data type and coverage, and the individual all impact estimates of the mutation rate. Despite these stochastic effects, we inferred that base pair mutation rates for all species fell between 0.5 and 1.4e-08 per generation per base pair (mean 0.81e-08 {+/-} 0.35-08 across Pantherinae). Our results provide a cautionary view on inter-species mutation rate comparisons, given the error associated with the reference genome choice and sequencing depth of coverage of the individuals.

evolutionary biology↗

bioRxiv2020

Epigenetic clock and methylation studies in elephants

Age-associated DNA-methylation profiles have been used successfully to develop highly accurate biomarkers of age ("epigenetic clocks") in humans, mice, dogs, and other species. Here we present epigenetic clocks for African and Asian elephants. These clocks were developed using novel DNA methylation profiles of 140 elephant blood samples of known age, at loci that are highly conserved between mammalian species, using a custom Infinium array (HorvathMammalMethylChip40). We present epigenetic clocks for Asian elephants (Elephas maximus), African elephants (Loxodonta africana), and both elephant species combined. Two additional human-elephant clocks were constructed by combing human and elephant samples. Epigenome-wide association studies identified elephant age-related CpGs and their proximal genes. The products of these genes play important roles in cellular differentiation, organismal development, metabolism, and circadian rhythms. Intracellular events observed to change with age included the methylation of bivalent chromatin domains, targets of polycomb repressive complexes, and TFAP2C binding sites. These readily available epigenetic clocks can be used for elephant conservation efforts where accurate estimates of age are needed to predict demographic trends.

developmental biology↗

bioRxiv2019

N-cadherin-Presented Slit Repulsive-Cues Direct Collective Schwann cell Migration

Collective cell migration is fundamental for the development of organisms and in the adult, for tissue regeneration and in pathological conditions such as cancer. Migration as a coherent group requires the maintenance of cell-cell interactions, while contact-inhibition-of-locomotion (CIL), a local repulsive force, propels the group forward. Here we show that the cell-cell interaction molecule, N-cadherin, regulates both adhesion and repulsion processes during Schwann cell collective migration, which is required for peripheral nerve regeneration. However, distinct from its role in cell-cell adhesion, the repulsion process is independent of N-cadherin trans-homodimerisation and the associated adherens junction complex. Rather, the extracellular domain of N-cadherin acts to traffic a repulsive Slit2/Slit3 signal to the cell-surface. Inhibiting Slit2/Slit3 signalling inhibits CIL and subsequently collective SC migration, resulting in adherent, non-migratory cell clusters. These findings provide insight into how opposing signals can mediate collective cell migration and how CIL pathways are promising targets for inhibiting pathological cell migration.

molecular biology↗