Browsing by Author "Marques, Mariana"
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- CRISPRi-mediated characterization of novel anti-tuberculosis targets: mycobacterial peptidoglycan modifications promote beta-lactam resistance and intracellular survivalPublication . Silveiro, Cátia; Marques, Mariana; Olivença, Francisco; Pires, David; Mortinho, Diana; Nunes, Alexandra; Pimentel, Madalena; Anes, Elsa; Catalão, Maria JoãoThe lack of effective therapeutics against emerging multi-drug resistant strains of Mycobacterium tuberculosis (Mtb) prompts the identification of novel anti-tuberculosis targets. The essential nature of the peptidoglycan (PG) layer of the mycobacterial cell wall, which features several distinctive modifications, such as the N-glycolylation of muramic acid and the amidation of D-iso-glutamate, makes it a target of particular interest. To understand their role in susceptibility to beta-lactams and in the modulation of host-pathogen interactions, the genes encoding the enzymes responsible for these PG modifications (namH and murT/gatD, respectively) were silenced in the model organism Mycobacterium smegmatis using CRISPR interference (CRISPRi). Although beta-lactams are not included in TB-therapy, their combination with beta-lactamase inhibitors is a prospective strategy to treat MDR-TB. To uncover synergistic effects between the action of beta-lactams and the depletion of these PG modifications, knockdown mutants were also constructed in strains lacking the major beta-lactamase of M. smegmatis BlaS, PM965 (M. smegmatis ΔblaS1) and PM979 (M. smegmatis ΔblaS1 ΔnamH). The phenotyping assays affirmed the essentiality of the amidation of D-iso-glutamate to the survival of mycobacteria, as opposed to the N-glycolylation of muramic acid. The qRT-PCR assays confirmed the successful repression of the target genes, along with few polar effects and differential knockdown level depending on PAM strength and target site. Both PG modifications were found to contribute to beta-lactam resistance. While the amidation of D-iso-glutamate impacted cefotaxime and isoniazid resistance, the N-glycolylation of muramic acid substantially promoted resistance to the tested beta-lactams. Their simultaneous depletion provoked synergistic reductions in beta-lactam MICs. Moreover, the depletion of these PG modifications promoted a significantly faster bacilli killing by J774 macrophages. Whole-genome sequencing revealed that these PG modifications are highly conserved in a set of 172 clinical strains of Mtb, demonstrating their potential as therapeutic targets against TB. Our results support the development of new therapeutic agents targeting these distinctive mycobacterial PG modifications.
- Effectiveness of psychological interventions in the treatment of perinatal depression: a systematic review of systematic reviews and meta-analysesPublication . Branquinho, Mariana; Rodriguez-Muñoz, María de la Fe; Maia, Berta Rodrigues; Marques, Mariana; Matos, Marcela; Osma, Jorge; Moreno-Peral, Patricia; Conejo-Cerón, Sonia; Fonseca, Ana; Vousoura, EleniBACKGROUND: Perinatal depression is a high prevalent mental health problem with serious consequences. Evidence about effective psychological interventions in treating perinatal depression has been increasing, but it lacks a comprehensive synthesis of findings. METHODS: A systematic review of systematic reviews and meta-analyses concerning the effectiveness of psychological interventions in treating perinatal depression (depression during pregnancy and the first 12 months postpartum) in adult women was conducted. The electronic databases MEDLINE (PubMed), PsycINFO, The Cochrane Library, Web of Science and Prospero were searched, on May 2020, using a combination of keywords. Data were independently extracted by two authors and a synthesis of the results was presented. Methodological quality was independently assessed by two authors, using AMSTAR-2. RESULTS: Seven systematic reviews were included and reported, overall, the effectiveness of psychological interventions in decreasing depressive symptoms in women in the perinatal period, both short and long-term. CBT was found to be the most effective intervention, regardless of the treatment format. LIMITATIONS: Grey literature was not searched, and some studies may overlap among the included systematic reviews. These (the included reviews) were rated with low methodological quality, which weakens the evidence of the reported results. CONCLUSIONS: CBT is currently the most evidence-based psychological intervention, provided in different delivery formats (individual, group, face-to-face or Internet-based). Further studies, including systematic reviews, with other types of psychological interventions (e.g., third-wave CBT) and with higher quality are needed.
- Influenza A virus propagation requires the activation of the unfolded protein response and the accumulation of insoluble protein aggregatesPublication . Marques, Mariana; Ramos, Bruno; Albuquerque, Hélio; Pereira, Marisa; Ribeiro, Diana Roberta; Nunes, Alexandre; Sarabando, Jéssica; Brás, Daniela; Ferreira, Ana Rita; Vitorino, Rui; Amorim, Maria João; Silva, Artur M. S.; Soares, Ana Raquel; Ribeiro, DanielaInfluenza A virus (IAV) employs multiple strategies to manipulate cellular mechanisms and support proper virion formation and propagation. In this study, we performed a detailed analysis of the interplay between IAV and the host cells’ proteostasis throughout the entire infectious cycle. We reveal that IAV infection activates the inositol requiring enzyme 1 (IRE1) branch of the unfolded protein response, and that this activation is important for an efficient infection. We further observed the accumulation of virus-induced insoluble protein aggregates, containing both viral and host proteins, associated with a dysregulation of the host cell RNA metabolism. Our data indicate that this accumulation is important for IAV propagation and favors the final steps of the infection cycle, more specifically the virion assembly. These findings reveal additional mechanisms by which IAV disrupts host proteostasis and uncovers new cellular targets that can be explored for the development of host-directed antiviral strategies.
- Internet use patterns and the relation between generalized problematic internet use and psychological distress in Portuguese university studentsPublication . Maia, Berta Rodrigues; Marques, Mariana; Pereira, Ana Telma; Macedo, AntónioInternet use patterns, generalized problematic internet use, and the latter’s relation to psychological distress were explored in a sample of 503 university students (Mage = 20.25; SD = 2.75). A questionnaire about internet use patterns, the Generalized Problematic Internet Use Scale 2, and the Depression, Anxiety and Stress Scales were answered. The students spent 5 hours online on a daily basis. The total generalized problematic internet use index score corresponded to a medium-risk level, with 12.9% of men and 5.0% of women presenting a high-risk level. Higher total generalized problematic internet use risk levels corresponded to higher levels of depression, anxiety and stress. Our results seem to show that university students constitute a particularly vulnerable group in terms of problematic internet use, supporting the relation between generalized problematic internet use and psychological distress.