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Biology subjects

Catanzaro, A.

Publications and source records attributed to Catanzaro, A..

4 recordsLinked to original sources

Low-cost monophasic transcranial magnetic stimulator

Transcranial magnetic stimulation (TMS) excites neurons noninvasively by electromagnetic induction and is used in neurophysiology research and in approved therapy for depression. Commercial stimulators cost tens of thousands of dollars. Existing open-source designs are either low-energy and unvalidated or rely on expensive switches and laboratory infrastructure. We present a monophasic, fixed-pulse-shape TMS device built at a parts cost of ~USD 700 which, under specific modeling assumptions, can exceed average human motor thresholds. Our design assumes access to basic, off-the-shelf equipment such as a 24 V power supply unit, an oscilloscope, and a few basic tools. The device charges a 230 F film-capacitor bank and discharges it through a self-wound figure-of-eight coil using a thyristor, producing a fixed pulse with a positive lobe lasting approximately 90 s. A Zero-Voltage Switching (ZVS) driver-based charging circuit charges the capacitor bank up to 1460 V from a 24 V bench supply. Three galvanically isolated voltage domains, redundant interlocks, and passive and active discharge paths help mitigate the safety risks involved with handling lethal energy levels. We also present a low-cost way to characterize the device by reconstructing coil di/dt from pickup-coil dB/dt maps to estimate the induced cortical E-fields. At the maximum capacitor voltage, the recovered maximal di/dt is 110.86 A/s, giving estimated 99.9th percentile cortical E-fields of 159 V/m at Oz and 196 V/m at C3 on an example anatomy. Although not yet approved for clinical trials and routine stimulation, the device demonstrated the possibility of a cost-effective TMS unit.

bioengineering↗

Defining the transmission parameters of lumpy skin disease virus by the three model insect vector species Aedes aegypti, Stomoxys calcitrans and Culicoides nubeculosus reveals important differences in their likely role in transmission

Lumpy skin disease virus (LSDV) is a poxvirus that can cause severe, systemic disease in cattle. By far the most important route of transmission of LSDV is mechanical transmission via haematophagous arthropod vectors. However we lack detailed information on this process including the likelihood of transmission by different vector species. This study used an experimental bovine model of LSDV transmission to quantify the transmission of LSDV from an infected donor to a naive recipient calf. Three species of Diptera representing different vector groups were included (Stomoxys calcitrans, Aedes aegypti and Culicoides nubeculosus, respectively a large biting fly, a mosquito and a midge), and the clinical, virological and immunological outcomes in the recipient calves studied. The ability of Ae. aegypti to mechanically transmit LSDV following feeding on an artificial membrane feeding system was also examined. Both Ae. aegypti and S. calcitrans were able to transmit LSDV, resulting in disease in recipient calves. Bites from virus-positive C. nubeculosus did not result in disease in recipient calves, though the presence of neutralising antibodies in these recipients indicated exposure to virus or virus components. Ae. aegypti successfully transmitted LSDV following feeding on LSDV-spiked blood through an artificial membrane feeding system, validating this laboratory model as a future replacement for donor cattle. Mathematical models of the data were generated and predicted S. calcitrans to be the most efficient vector of LSDV of the insects tested with a reproduction number (R0) of 5.8. Impact statementLumpy skin disease virus (LSDV) is a neglected, rapidly emerging pathogen of cattle that has spread into Europe and throughout the Middle East and Asia over the past ten years. Lack of understanding of the mechanism of transmission of LSDV has hampered efforts to control its rapid spread. This study compares the ability of three model species of Diptera (Stomoxys calcitrans, Aedes aegypti and Culicoides nubeculosus) to mechanically transmit the virus to cattle, generating high quality quantitative data to facilitate mathematical modelling of virus transmission. S. calcitrans was identified as a potential driver of LSDV transmission with a R0 of 5.8. This work provides new insights into the vector transmission of LSDV that can be used to design more targeted and effective disease control programmes.

microbiology↗

Minimal immune cell subset differences in a cohort of close contacts of tuberculosis index cases

Understanding the perturbations in immune response across the spectrum of TB infection is still unclear. In this study, we followed a cohort of close contacts of pulmonary TB patients with serial QFT testing at 0, 3, 6, and 12 months, and stratified them into six subgroups: QFT-increasing (low/high), QFT converters (QFT- to QFT+), QFT+ stable, and QFT- individuals. Despite these distinct QFT trajectories, we observed minimal differences in immune cell frequencies, activation profiles, and T helper subset distributions among the QFT subgroups, suggesting limited immunological stratification based on QFT dynamics alone. Ex vivo immune phenotyping, including analysis of CD4, CD8, and NKT cell frequencies, memory T cell subsets, and activated T cells (HLA-DRCD38), failed to distinguish between QFT subgroups. Antigen-specific CD4 T cell responses assessed by the activation-induced marker (AIM) assay were elevated in QFT+ compared to QFT- individuals. These findings suggest that blood-based immune profiling may not capture subtle immunological transitions among QFT converters or individuals with increasing QFT responses. In contrast, individuals with active TB (ATB) showed clear immune perturbations. ATB patients at diagnosis exhibited significantly elevated frequencies of antigen-specific CD4 T cells, increased activated T cells, and higher frequencies of intermediate monocytes and NK cells compared to QFT+/QFT- contacts. Many of these immune features declined with treatment, indicating therapy-associated immune resolution. Additionally, shifts in T helper subsets and effector memory populations were observed over the course of treatment. These results suggest that while ex vivo immune profiling can robustly distinguish active TB from non-diseased states, it lacks the resolution to differentiate QFT subgroups based on QFT dynamics alone. This could reflect either immunological similarity among close contacts regardless of QFT status or limitations of blood-based phenotyping in detecting early or subclinical immune shifts. Our study highlights the challenge of immunologically distinguishing QFT-defined subgroups within close contacts using conventional ex vivo profiling approaches.

immunology↗

Identification of differentially recognized T cell epitopes in the spectrum of Mtb infection

Tuberculosis caused by Mycobacterium tuberculosis is one of the leading causes of death from a single infectious agent. Identifying dominant epitopes and comparing their reactivity in different tuberculosis (TB) infection states can help design diagnostics and vaccines. We performed a proteome-wide screen of 20,610 Mtb derived peptides in 21 Active TB (ATB) patients 3-4 months post-diagnosis of pulmonary TB (mid-treatment) using an IFN{gamma} and IL-17 Fluorospot assay. Responses were mediated exclusively by IFN{gamma} and identified a total of 137 unique epitopes, with each patient recognizing, on average, 8 individual epitopes and 22 epitopes (16%) recognized by 2 or more participants. Responses were predominantly directed against antigens part of the cell wall and cell processes category. Testing 517 peptides spanning TB vaccine candidates and ESAT- 6 and CFP10 antigens also revealed differential recognition between ATB participants mid-treatment and healthy IGRA+ participants of several vaccine antigens. An ATB-specific peptide pool consisting of epitopes exclusively recognized by participants mid-treatment, allowed distinguishing participants with active pulmonary TB from healthy interferon-gamma release assay (IGRA)+/- participants from diverse geographical locations. Analysis of longitudinal samples indicated decreased reactivity during treatment for pulmonary TB. Together, these results show that a proteome-wide screen of T cell reactivity identifies epitopes and antigens that are differentially recognized depending on the Mtb infection stage. These have potential use in developing diagnostics and vaccine candidates and measuring correlates of protection.

immunology↗