Biology subjects

Marino, C.

Publications and source records attributed to Marino, C..

6 recordsLinked to original sources

bioRxiv2025

Conjugates of α-d-Galp-(1->3)-β-d-Galp for the serological diagnosis of Chagas disease.

BackgroundChagas disease (ChD), caused by the parasitic protozoan Trypanosoma cruzi, is a lifelong, neglected tropical disease with substantial medical and socioeconomic impact. Despite this situation, currently available diagnostic and therapeutic methods display serious limitations. A promising strategy to improve ChD serodiagnosis involves targeting parasite carbohydrate antigens, particularly the -galactosyl-rich mucins that coat the surface of bloodstream trypomastigotes (tGPI-mucins). Methods/Principle FindingsHere, we present a concise and efficient protocol for the chemical synthesis of a tGPI-mucin-derived glycotope, the disaccharide -O_SCPLOWDC_SCPLOW-Galp-(1[->]3)-{beta}-O_SCPLOWDC_SCPLOW-Galp, and its functional conjugation to different scaffolds using the squarate method. A neoglycoprotein made upon a bovine serum albumin (BSA) carrier decorated with [~]28 units of the disaccharide, termed BSA-Di, was interrogated with sera of chronic ChD patients and healthy individuals from Argentina using an in-house enzyme-linked immunosorbent assay (ELISA). BSA-Di exhibited excellent sensitivity and effectively discriminated between ChD-positive and negative sera with high accuracy (AUC = 0.905), though its specificity was partially affected by cross-reactivity of some non-ChD sera containing natural -Gal antibodies. Conjugation of -O_SCPLOWDC_SCPLOW-Galp-(1[->]3)-{beta}-O_SCPLOWDC_SCPLOW-Galp to T. cruzi antigenic peptides, instead of BSA, corroborated these findings and enabled the generation of bivalent ChD diagnostic reagents combining glycan- and peptide-based epitopes. Conclusions/SignificanceOverall, our results identify -O_SCPLOWDC_SCPLOW-Galp-(1[->]3)-{beta}-O_SCPLOWDC_SCPLOW-Galp as a robust and reliable biomarker of T. cruzi infection. The methodologies and tools described here, together with optimized derivatives, are expected to positively impact ChD serological applications. AUTHOR SUMMARYDespite the enormous burden imposed by Chagas disease, diagnostic and therapeutic methods still present serious deficiencies. Towards filling this gap, we herein developed a protocol for the chemical synthesis of -O_SCPLOWDC_SCPLOW-Galp-(1[->]3)-{beta}-O_SCPLOWDC_SCPLOW-Galp, a major glycotope present on the Trypanosoma cruzi surface coat. This disaccharide was conjugated with different molecular scaffolds and serologically evaluated using an in-house enzyme-linked immunosorbent assay (ELISA). Our results indicate that -O_SCPLOWDC_SCPLOW-Galp-(1[->]3)-{beta}-O_SCPLOWDC_SCPLOW-Galp provides an overall robust and reliable biomarker of T. cruzi infection, with excellent sensitivity and only minor concerns regarding its potential cross-reactivity with natural -Gal antibodies. These findings indicate that the tools developed here, as well as optimized versions derived from them, should have a positive impact on the diagnosis and clinical management of Chagas disease and on the identification and/or clinical validation of novel drug/vaccine candidates for the treatment of T. cruzi infections.

microbiology↗

bioRxiv2025

Analyzing nicotine action against amyloid toxicity by NMR-pharmacometabolomics: an exploratory study.

Alzheimers disease (AD) is the primary neurodegenerative disease spread worldwide. One of the main histopathological hallmarks of AD is amyloid plaque deposition in the brain. Despite some epidemiological studies demonstrating that cigarette smoke is a factor in predisposing people to AD, nicotine, the principal alkaloid of Nicotiana Tobacco, has been widely studied for its ability to improve cognitive performance, both in animal models and in human studies. Several hypotheses have been proposed to explain the mechanism of action underlying the beneficial effect of Nicotine in AD; however, this is still questioned. To have new insights into the molecular mechanism underlying the neuroprotective action of Nicotine in Alzheimers disease, we performed an NMR metabolomic analysis of SH-SY5Y neuroblastoma cells treated with A{beta} (1-42) in the presence of nicotine. Our data show that the neuroprotective action of nicotine resides in its ability to restore the systemic unbalanced metabolism associated with AD. In particular, nicotine reverses most A{beta} (1-42)-induced metabolic impairments, including those related to amino acid metabolism, especially those involved in neurotransmission, as well as alterations in energy metabolism and membrane phospholipid metabolism.

cell biology↗

bioRxiv2025

Strategic citations for a fairer academic landscape

Scientific publishing is increasingly dominated by for-profit journals, which attract prestige and submissions through high impact factors (IF). While some of these partly reinvest in research and dissemination and can be considered academia-friendly, non-profit journals - those that fully reinvest revenue into the academic community - often struggle for visibility despite promoting more equitable publishing models. Using citation data from over 70,000 publications in ecology and evolution, we show that citation practices are siloed: for-profit journals disproportionately cite other for-profit journals, academia-friendly journals preferentially cite other academia-friendly journals, and non-profit journals likewise favor citations to non-profit sources. This asymmetry structurally reinforces the IF advantage of for-profit journals simply because they are dominant in the publishing system. To address this inequity, we propose a soft-power, low-risk approach of "strategic citation". By deliberately choosing to cite relevant articles from non-profit journals when multiple references would be equally valid, researchers can contribute to increasing those journals visibility and IF. This approach preserves scientific rigor and does not restrict publishing choices, but adds a layer of ethical intentionality to citation practices. Strategic citation offers a practical, actionable lever for researchers to promote a more balanced and ethical publishing system that complements broader structural reforms.

ecology↗

bioRxiv2025

RNase H1 counteracts DNA damage and ameliorates SMN-dependent phenotypes in a Drosophila model of Spinal Muscular Atrophy

Spinal Muscular Atrophy (SMA) is caused by a deficiency of the Survival Motor Neuron (SMN) protein. Mutations in SMN disrupt mRNA splicing and translation, leading to maladaptive changes in transcriptomes, proteomes, neuroinflammation, and metabolism, which drive motor neuron degeneration in SMA patients. Using a Drosophila SMA model, we found that systemic depletion of Smn leads to accumulation of RNA:DNA hybrids (R-loops), increased DNA damage, dysregulation of amino acids and sugar metabolism and activation of the innate immune response, recapitulating key pathological features reported in mammalian models and severe SMA patients. Persistent DNA damage in Smn-deficient flies alters cell proliferation rates in larval brains and induces extensive cell death in the developing eye. Importantly here, we show that stimulating the resolution of RNA:DNA hybrids with transgenic human RNAse H1 prevents the accumulation of DNA damage and attenuates the transcriptome and amino acid alterations induced by Smn depletion, mitigating the Smn-dependent cellular and developmental abnormalities, in Smn-deficient flies. Our data suggest that depletion of Smn causes an accumulation of aberrant transcripts and chronic DNA damage, which--along with the altered metabolomic profiles associated with Smn deficiency--trigger systemic inflammatory responses, ultimately affecting neuronal function and survival.

genetics↗

bioRxiv2024

Modeling suggests SARS-CoV-2 rebound after nirmatrelvir-ritonavir treatment is driven by target cell preservation coupled with incomplete viral clearance

In a subset of SARS-CoV-2 infected individuals treated with the oral antiviral nirmatrelvir-ritonavir, the virus rebounds following treatment. The mechanisms driving this rebound are not well understood. We used a mathematical model to describe the longitudinal viral load dynamics of 51 individuals treated with nirmatrelvir-ritonavir, 20 of whom rebounded. Target cell preservation, either by a robust innate immune response or initiation of nirmatrelvir-ritonavir near the time of symptom onset, coupled with incomplete viral clearance, appear to be the main factors leading to viral rebound. Moreover, the occurrence of viral rebound is likely influenced by time of treatment initiation relative to the progression of the infection, with earlier treatments leading to a higher chance of rebound. Finally, our model demonstrates that extending the course of nirmatrelvir-ritonavir treatment, in particular to a 10-day regimen, may greatly diminish the risk for rebound in people with mild-to-moderate COVID-19 and who are at high risk of progression to severe disease. Altogether, our results suggest that in some individuals, a standard 5-day course of nirmatrelvir-ritonavir starting around the time of symptom onset may not completely eliminate the virus. Thus, after treatment ends, the virus can rebound if an effective adaptive immune response has not fully developed. These findings on the role of target cell preservation and incomplete viral clearance also offer a possible explanation for viral rebounds following other antiviral treatments for SARS-CoV-2. ImportanceNirmatrelvir-ritonavir is an effective treatment for SARS-CoV-2. In a subset of individuals treated with nirmatrelvir-ritonavir, the initial reduction in viral load is followed by viral rebound once treatment is stopped. We show the timing of treatment initiation with nirmatrelvir-ritonavir may influence the risk of viral rebound. Nirmatrelvir-ritonavir stops viral growth and preserves target cells but may not lead to full clearance of the virus. Thus, once treatment ends, if an effective adaptive immune response has not adequately developed, the remaining virus can lead to rebound. Our results provide insights into the mechanisms of rebound and can help develop better treatment strategies to minimize this possibility.

immunology↗

bioRxiv2024

Predicting the global economic costs of biological invasions by tetrapods

Globalisation has steadily accelerated rates of biological invasions worldwide, leading to widespread environmental perturbations that often translate into rapidly expanding socioeconomic costs. Although such monetary costs can be estimated based on the observed effects of invasions, the pathways that lead invasive species to become economically impactful remain poorly understood. Here, we implement the first global-scale test of the hypothesis that adaptive traits that influence demographic resilience predict economic costs, using invasive terrestrial vertebrates as models given their rising impacts and well-catalogued characteristics. Our results reveal that total global costs of invasive tetrapods are conservatively in the tens of billions of dollars, with the vast majority due to damage costs from invasive mammals. These monetary impacts are predicted by longevity, female maturation age, diet and invasional pathway traits, although the directionality of predicted economic impacts also varied by trait across classes. Alarmingly, costs remain unknown for >90% of recorded established alien tetrapods worldwide, and across the majority of invaded countries. These huge socio-economic costs demonstrate the necessity of mitigating tetrapod invasions and filling knowledge gaps. Effective identification of traits predictive of costs among and within these groups can facilitate the prioritisation of resources to efficiently target the most damaging existing and emerging invasive tetrapod species.

ecology↗