NanoSOSG: A Nanostructured Fluorescent Probe for the Detection of Intracellular Singlet Oxygen

A biocompatible fluorescent nanoprobe for singlet oxygen (1O2) detection in biological systems was designed, synthesized, and characterized, that circumvents many of the limitations of the molecular probe Singlet Oxygen Sensor Green® (SOSG). This widely used commercial singlet oxygen probe was covalently linked to a polyacrylamide nanoparticle core using different architectures to optimize the response to 1O2. In contrast to its molecular counterpart, the optimum SOSG-based nanoprobe, which we call NanoSOSG, is readily internalized by E. coli cells and does not interact with bovine serum albumin. Furthermore, the spectral characteristics do not change inside cells, and the probe responds to intracellularly generated 1O2 with an increase in fluorescence

Abscisic Acid Insensitive 4 transcription factor is an important player in the response of Arabidopsis thaliana to two-spotted spider mite (Tetranychus urticae) feeding.

Plants growing in constantly changeable environmental conditions are compelled to evolve regulatory mechanisms to cope with biotic and abiotic stresses. Effective defence to invaders is largely connected with phytohormone regulation, resulting in the production of numerous defensive proteins and specialized metabolites. In our work, we elucidated the role of the Abscisic Acid Insensitive 4 (ABI4) transcription factor in the plant response to the two-spotted spider mite (TSSM). This polyphagous mite is one of the most destructive herbivores, which sucks mesophyll cells of numerous crop and wild plants. Compared to the wild-type (Col-0) Arabidopsis thaliana plants, the abi4 mutant demonstrated increased susceptibility to TSSM, reflected as enhanced female fecundity and greater frequency of mite leaf damage after trypan blue staining. Because ABI4 is regarded as an important player in the plastid-to-nucleus retrograde signalling process, we investigated the plastid envelope membrane dynamics using stroma-associated fluorescent marker. Our results indicated a clear increase in the number of stroma-filled tubular structures deriving from the plastid membrane (stromules) in the close proximity of the site of mite leaf damage, highlighting the importance of chloroplast-derived signals in the response to TSSM feeding activity

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

Background: We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods: We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results: No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions: Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old

Deep Learning Based Non-invasive Meningitis Screening Using High-Resolution Ultrasound in Neonates and Infants from Mozambique, Spain and Morocco

1st MICCAI Meets Africa Workshop, MImA 2024 and 1st MICCAI Student Board Workshop on Empowering Medical Information Computing and Research through Early-Career Expertise, EMERGE 2024, Held in Conjunction with MICCAI 2024. Medical Information Computing. MImA EMERGE 2024 2024. Communications in Computer and Information Science, vol 2240.Meningitis is a life-threatening disease, resulting in severe neurological damage or death if not treated in time. The standard diagnostic method is an invasive lumbar puncture (LP), not exempt of complications and not always feasible, especially in resource-poor settings. To overcome these challenges, we developed Neosonics®, a novel non-invasive high-resolution ultrasound (HRUS) technology that detects backscatter signals from white blood cells (WBCs) in cerebrospinal fluid (CSF) below the infant fontanel. Using deep learning (DL) for image analysis, this technology classifies patients based on WBC levels, providing a rapid, non-invasive screening method for infant meningitis and with this, limiting indications for LPs for positive cases only, if not contraindicated. A convolutional neural network was trained and validated using CSF HRUS patient data gathered from cohorts from three different countries, Mozambique, Spain and Morocco. Then, a soft voting ensemble-learning technique was applied to give a classification on a patient-level. The DL model showed on a single-image level a sensitivity (SE) and specificity (SP) of 71.1% and 87.0% for the Mozambican cohort, SE = 73.3% and SP = 75.5% for the Spanish cohort, and SE = 72.0% and SP = 88.7% for the Moroccan cohort. On a patient-level, the overall SE and SP was 94.4% and 94.8%, respectively. We demonstrate in this study the significance of combining HRUS and DL for the non-invasive detection of infant meningitis, offering an efficient, cost-effective solution suitable also for limited resource settings and remote areas.Kriba acknowledges support from the European Union’s Horizon Europe research and innovation programme, project code 190155553 - NEOSONICS. All authors with ISGlobal affiliation acknowledge support from the grant CEX2018-000806-S funded by MCIN/AEI/ https://doi.org/10.13039/501100011033, and support from the Generalitat de Catalunya through the CERCA Program. Mozambique: This work was supported by the Bill & Melinda Gates Foundation INV-048197. Morocco: This project was supported in part by Spanish Agency of Cooperation (AECID) under the reference number 2019/ACDE/001196. Project PI16/01822 from PI ENRIQUE BASSAT ORELLANA and project PI16/00738 funded by Instituto de Salud Carlos III, co-funded by the European Union (FEDER) “Una manera de hacer Europa”.Peer reviewe

Detection of human Betaherpesvirinae in saliva and urine from immunocompromised and immunocompetent subjects

Human cytomegalovirus (HCMV) is a well-known opportunistic agent that reactivates in human immunodeficiency virus (HIV)-seropositive subjects. Human herpesvirus 6 (HHV-6) and HHV-7 were discovered recently and, like HCMV, belong to the Betaherpesvirinae subfamily. We looked for the presence of HCMV, HHV-6, and HHV-7 by PCR with saliva and urine samples from 125 HIV-seropositive patients at different stages of HIV infection and with saliva and urine samples from 29 HIV-seronegative subjects. All three viruses were frequently detected in the saliva (overall rates of detection, 61, 43, and 63% for HCMV, HHV-6, and HHV-7, respectively) with no correlation with the stage of immune deficiency. In contrast, HCMV was detected in urine much more frequently than the two other herpesviruses (overall rates of detection, 37, 2, and 6.5% for HCMV, HHV-6, and HHV-7, respectively) and was associated with immune deficiency. This suggests that these three genetically related viruses differ from each other with regard to replication in the urinary tract.</jats:p