17 results on '"Mambretti F"'
Search Results
2. Efficiency and controllability of stochastic boolean function generation by a random network of non-linear nanoparticle junctions.
- Author
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Martini, G., Tentori, E., Mirigliano, M., Galli, D. E., Milani, P., Mambretti, F., Moretti, Paolo, and Cusick, Thomas
- Subjects
BOOLEAN functions ,NANOPARTICLES ,BIOLOGICAL neural networks ,GOLD films ,SEARCH algorithms - Abstract
Amid efforts to address energy consumption in modern computing systems, one promising approach takes advantage of random networks of non-linear nanoscale junctions formed by nanoparticles as substrates for neuromorphic computing. These networks exhibit emergent complexity and collective behaviors akin to biological neural networks, characterized by self-organization, redundancy, and non-linearity. Based on this foundation, a generalization of n-inputs devices has been proposed, where the associated weights depend on all the input values. This model, called receptron, has demonstrated its capability to generate Boolean functions as output, representing a significant breakthrough in unconventional computing methods. In this work, we characterize and present two actual implementations of this paradigm. One approach leverages the nanoscale properties of cluster-assembled Au films, while the other utilizes the recently introduced Stochastic Resistor Network (SRN) model. We first provide a concise overview of the electrical properties of these systems, emphasizing the insights gained from the SRN regarding the physical processes within real nanostructured gold films at a coarse-grained scale. Furthermore, we present evidence indicating the minimum complexity level required by the SRN model to achieve a stochastic dynamics adequate to effectively model a novel component for logic systems. To support our argument that these systems are preferable to conventional random search algorithms, we discuss quantitative criteria based on Information-theoretic tools. This suggests a practical means to steer the stochastic dynamics of the system in a controlled way, thus focusing its random exploration where it is most useful. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
3. Maternal and infant NR3C1 and SLC6A4 epigenetic signatures of the COVID-19 pandemic lockdown: when timing matters
- Author
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Nazzari, S, Grumi, S, Mambretti, F, Villa, M, Giorda, R, Provenzi, L, Borgatti, R, Biasucci, G, Decembrino, L, Giacchero, R, Magnani, M, Nacinovich, R, Prefumo, F, Spinillo, A, Veggiotti, P, Nazzari S., Grumi S., Mambretti F., Villa M., Giorda R., Provenzi L., Borgatti R., Biasucci G., Decembrino L., Giacchero R., Magnani M. L., Nacinovich R., Prefumo F., Spinillo A., Veggiotti P., Nazzari, S, Grumi, S, Mambretti, F, Villa, M, Giorda, R, Provenzi, L, Borgatti, R, Biasucci, G, Decembrino, L, Giacchero, R, Magnani, M, Nacinovich, R, Prefumo, F, Spinillo, A, Veggiotti, P, Nazzari S., Grumi S., Mambretti F., Villa M., Giorda R., Provenzi L., Borgatti R., Biasucci G., Decembrino L., Giacchero R., Magnani M. L., Nacinovich R., Prefumo F., Spinillo A., and Veggiotti P.
- Abstract
Stress exposure during pregnancy is critically linked with maternal mental health and child development. The effects might involve altered patterns of DNA methylation in specific stress-related genes (i.e., glucocorticoid receptor gene, NR3C1, and serotonin transporter gene, SLC6A4) and might be moderated by the gestational timing of stress exposure. In this study, we report on NR3C1 and SLC6A4 methylation status in Italian mothers and infants who were exposed to the COVID-19 pandemic lockdown during different trimesters of pregnancy. From May 2020 to February 2021, 283 mother–infant dyads were enrolled at delivery. Within 24 h from delivery, buccal cells were collected to assess NR3C1 (44 CpG sites) and SLC6A4 (13 CpG sites) methylation status. Principal component (PC) analyses were used to reduce methylation data dimension to one PC per maternal and infant gene methylation. Mother–infant dyads were split into three groups based on the pregnancy trimester (first, second, third), during which they were exposed to the COVID-19 lockdown. Mothers and infants who were exposed to the lockdown during the first trimester of pregnancy had lower NR3C1 and SLC6A4 methylation when compared to counterparts exposed during the second or third trimesters. The effect remained significant after controlling for confounders. Women who were pregnant during the pandemic and their infants might present altered epigenetic biomarkers of stress-related genes. As these epigenetic marks have been previously linked with a heightened risk of maternal psychiatric problems and less-than-optimal child development, mothers and infants should be adequately monitored for psychological health during and after the pandemic.
- Published
- 2022
4. Sex-dependent association between variability in infants’ OXTR methylation at birth and negative affectivity at 3 months
- Author
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Nazzari, S, Grumi, S, Villa, M, Mambretti, F, Biasucci, G, Decembrino, L, Giacchero, R, Magnani, M, Nacinovich, R, Prefumo, F, Spinillo, A, Veggiotti, P, Fullone, E, Giorda, R, Provenzi, L, Nazzari S., Grumi S., Villa M., Mambretti F., Biasucci G., Decembrino L., Giacchero R., Magnani M. L., Nacinovich R., Prefumo F., Spinillo A., Veggiotti P., Fullone E., Giorda R., Provenzi L., Nazzari, S, Grumi, S, Villa, M, Mambretti, F, Biasucci, G, Decembrino, L, Giacchero, R, Magnani, M, Nacinovich, R, Prefumo, F, Spinillo, A, Veggiotti, P, Fullone, E, Giorda, R, Provenzi, L, Nazzari S., Grumi S., Villa M., Mambretti F., Biasucci G., Decembrino L., Giacchero R., Magnani M. L., Nacinovich R., Prefumo F., Spinillo A., Veggiotti P., Fullone E., Giorda R., and Provenzi L.
- Abstract
Background: Sex-specific differences in DNA methylation of the oxytocin receptor gene (OXTR) have been shown in adults and are related to several mental disorders. Negative affectivity early in life is a trans-diagnostic risk marker of later psychopathology and is partly under genetic control. However, sex-specific variations in OXTR methylation (OXTRm) in infants and their associations with negative affectivity are still unknown. Aims: Here, we explored sex differences in the association between infant OXTRm at birth and negative affectivity at 3 months of age. Methods: Infants and their mothers (N = 224) were recruited at delivery. Infants’ methylation status was assessed in 13 CpG sites within the OXTR gene intron 1 region (chr3: 8810654–8810919) in buccal cells at birth while 3-month-old infants’ negative affectivity was assessed by mothers using a well-validated temperament questionnaire. Results: OXTRm at 12 CpG sites was higher in females than in males. Moreover, higher infants’ OXTRm at 6 specific CpG sites was associated with greater negative affectivity in males, but not in females. Conclusions: These results provide new insights into the role of sex-dependent epigenetic mechanisms linking OXTRm with early infants’ emotional development. Understanding the degree to which epigenetic processes relate to early temperamental variations may help inform the etiology of later childhood psychopathological outcomes.
- Published
- 2022
5. Is Brain-Derived Neurotropic Factor Methylation Involved in the Association Between Prenatal Stress and Maternal Postnatal Anxiety During the COVID-19 Pandemic?
- Author
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Provenzi, L, Villa, M, Mambretti, F, Citterio, A, Grumi, S, Bertazzoli, E, Biasucci, G, Decembrino, L, Gardella, B, Giacchero, R, Magnani, M, Nacinovich, R, Pisoni, C, Prefumo, F, Orcesi, S, Scelsa, B, Giorda, R, Borgatti, R, Provenzi, Livio, Villa, Marco, Mambretti, Fabiana, Citterio, Andrea, Grumi, Serena, Bertazzoli, Emanuela, Biasucci, Giacomo, Decembrino, Lidia, Gardella, Barbara, Giacchero, Roberta, Magnani, Maria Luisa, Nacinovich, Renata, Pisoni, Camilla, Prefumo, Federico, Orcesi, Simona, Scelsa, Barbara, Giorda, Roberto, Borgatti, Renato, Provenzi, L, Villa, M, Mambretti, F, Citterio, A, Grumi, S, Bertazzoli, E, Biasucci, G, Decembrino, L, Gardella, B, Giacchero, R, Magnani, M, Nacinovich, R, Pisoni, C, Prefumo, F, Orcesi, S, Scelsa, B, Giorda, R, Borgatti, R, Provenzi, Livio, Villa, Marco, Mambretti, Fabiana, Citterio, Andrea, Grumi, Serena, Bertazzoli, Emanuela, Biasucci, Giacomo, Decembrino, Lidia, Gardella, Barbara, Giacchero, Roberta, Magnani, Maria Luisa, Nacinovich, Renata, Pisoni, Camilla, Prefumo, Federico, Orcesi, Simona, Scelsa, Barbara, Giorda, Roberto, and Borgatti, Renato
- Abstract
Background: The COVID-19 pandemic is a collective trauma that may expose susceptible individuals to high levels of stress. Pregnant women represent a high-risk population, considering that pregnancy is a period of heightened neuroplasticity and susceptibility to stress through epigenetic mechanisms. Previous studies showed that the methylation status of the BDNF gene is linked with prenatal stress exposure. The goals of this study were (a) to assess the association between pandemic-related stress and postnatal anxiety and (b) to investigate the potential role of maternal BDNF methylation as a significant mediator of this association. Methods: In the present study, we report data on the association among pandemic-related stress during pregnancy, maternal BDNF methylation, and postnatal anxiety symptoms. Pandemic-related stress and postnatal anxiety were assessed through self-report instruments. BDNF methylation was estimated in 11 CpG sites in DNA from mothers’ buccal cells. Complete data were available from 108 mothers. Results: Results showed that pandemic-related stress was associated with an increased risk of postnatal anxiety, r = 0.20, p < 0.05. CpG-specific BDNF methylation was significantly associated with both prenatal pandemic-related stress, r = 0.21, p < 0.05, and postnatal maternal anxious symptoms, r = 0.25, p = 0.01. Moreover, a complete mediation by the BDNF CpG6 methylation emerged between pandemic-related stress during pregnancy and postnatal maternal anxiety, ACME = 0.66, p < 0.05. Conclusion: These findings suggest that BDNF epigenetic regulation by pandemic-related stress might contribute to increase the risk of anxiety in mothers. Policymakers should prioritize the promotion of health and wellbeing in pregnant women and mothers during the present healthcare emergency.
- Published
- 2022
6. The hidden pandemic: COVID-19-related stress, SLC6A4 methylation, and infants' temperament at 3 months
- Author
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Provenzi, L, Mambretti, F, Villa, M, Grumi, S, Citterio, A, Bertazzoli, E, Biasucci, G, Decembrino, L, Falcone, R, Gardella, B, Longo, R, Nacinovich, R, Pisoni, C, Prefumo, F, Orcesi, S, Scelsa, B, Giorda, R, Borgatti, R, Provenzi, L, Mambretti, F, Villa, M, Grumi, S, Citterio, A, Bertazzoli, E, Biasucci, G, Decembrino, L, Falcone, R, Gardella, B, Longo, R, Nacinovich, R, Pisoni, C, Prefumo, F, Orcesi, S, Scelsa, B, Giorda, R, and Borgatti, R
- Abstract
The COVID‐19 pandemic represents a collective trauma that may have enduring stress effects during sensitive periods, such as pregnancy. Prenatal stress may result in epigenetic signatures of stress‐related genes (e.g., the serotonin transporter gene, SLC6A4) that may in turn influence infants’ behavioral development. In April 2020, we launched a longitudinal cohort study to assess the behavioral and epigenetic vestiges of COVID‐19‐related prenatal stress exposure in mothers and infants. COVID‐19‐related prenatal stress was retrospectively assessed at birth. SLC6A4 methylation was assessed in thirteen CpG sites in mothers and infants’ buccal cells. Infants’ temperament was assessed at 3‐month‐age. Complete data were available from 108 mother‐infant dyads. Greater COVID‐19‐related prenatal stress was significantly associated with higher infants’ SLC6A4 methylation in seven CpG sites. SLC6A4 methylation at these sites predicted infants’ temperament at 3 months.
- Published
- 2021
7. The MRX complex regulates Exo1 resection activity by altering DNA end structure
- Author
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Gobbini, E, Cassani, C, Vertemara, J, Wang, W, Mambretti, F, Casari, E, Sung, P, Tisi, R, Zampella, G, Longhese, M, Gobbini, Elisa, Cassani, Corinne, Vertemara, Jacopo, Wang, Weibin, Mambretti, Fabiana, CASARI, ERIKA, Sung, Patrick, Tisi, Renata, Zampella, Giuseppe, Longhese, Maria Pia, Gobbini, E, Cassani, C, Vertemara, J, Wang, W, Mambretti, F, Casari, E, Sung, P, Tisi, R, Zampella, G, Longhese, M, Gobbini, Elisa, Cassani, Corinne, Vertemara, Jacopo, Wang, Weibin, Mambretti, Fabiana, CASARI, ERIKA, Sung, Patrick, Tisi, Renata, Zampella, Giuseppe, and Longhese, Maria Pia
- Abstract
Homologous recombination is triggered by nucleolytic degradation (resection) of DNA double-strand breaks (DSBs). DSB resection requires the Mre11-Rad50-Xrs2 (MRX) complex, which promotes the activity of Exo1 nuclease through a poorly understood mechanism. Here, we describe the Mre11-R10T mutant variant that accelerates DSB resection compared to wild-type Mre11 by potentiating Exo1-mediated processing. This increased Exo1 resection activity leads to a decreased association of the Ku complex to DSBs and an enhanced DSB resection in G1, indicating that Exo1 has a direct function in preventing Ku association with DSBs. Molecular dynamics simulations show that rotation of the Mre11 capping domains is able to induce unwinding of double-strand DNA (dsDNA). The R10T substitution causes altered orientation of the Mre11 capping domain that leads to persistent melting of the dsDNA end. We propose that MRX creates a specific DNA end structure that promotes Exo1 resection activity by facilitating the persistence of this nuclease on the DSB ends, uncovering a novel MRX function in DSB resection
- Published
- 2018
8. Is Brain-Derived Neurotropic Factor Methylation Involved in the Association Between Prenatal Stress and Maternal Postnatal Anxiety During the COVID-19 Pandemic?
- Author
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Livio Provenzi, Marco Villa, Fabiana Mambretti, Andrea Citterio, Serena Grumi, Emanuela Bertazzoli, Giacomo Biasucci, Lidia Decembrino, Barbara Gardella, Roberta Giacchero, Maria Luisa Magnani, Renata Nacinovich, Camilla Pisoni, Federico Prefumo, Simona Orcesi, Barbara Scelsa, Roberto Giorda, Renato Borgatti, Provenzi, L, Villa, M, Mambretti, F, Citterio, A, Grumi, S, Bertazzoli, E, Biasucci, G, Decembrino, L, Gardella, B, Giacchero, R, Magnani, M, Nacinovich, R, Pisoni, C, Prefumo, F, Orcesi, S, Scelsa, B, Giorda, R, and Borgatti, R
- Subjects
Psychiatry and Mental health ,BDNF ,pandemic ,stre ,COVID-19 ,methylation ,pregnancy ,anxiety ,epigenetic - Abstract
BackgroundThe COVID-19 pandemic is a collective trauma that may expose susceptible individuals to high levels of stress. Pregnant women represent a high-risk population, considering that pregnancy is a period of heightened neuroplasticity and susceptibility to stress through epigenetic mechanisms. Previous studies showed that the methylation status of the BDNF gene is linked with prenatal stress exposure. The goals of this study were (a) to assess the association between pandemic-related stress and postnatal anxiety and (b) to investigate the potential role of maternal BDNF methylation as a significant mediator of this association.MethodsIn the present study, we report data on the association among pandemic-related stress during pregnancy, maternal BDNF methylation, and postnatal anxiety symptoms. Pandemic-related stress and postnatal anxiety were assessed through self-report instruments. BDNF methylation was estimated in 11 CpG sites in DNA from mothers’ buccal cells. Complete data were available from 108 mothers.ResultsResults showed that pandemic-related stress was associated with an increased risk of postnatal anxiety, r = 0.20, p < 0.05. CpG-specific BDNF methylation was significantly associated with both prenatal pandemic-related stress, r = 0.21, p < 0.05, and postnatal maternal anxious symptoms, r = 0.25, p = 0.01. Moreover, a complete mediation by the BDNF CpG6 methylation emerged between pandemic-related stress during pregnancy and postnatal maternal anxiety, ACME = 0.66, p < 0.05.ConclusionThese findings suggest that BDNF epigenetic regulation by pandemic-related stress might contribute to increase the risk of anxiety in mothers. Policymakers should prioritize the promotion of health and wellbeing in pregnant women and mothers during the present healthcare emergency.
- Published
- 2022
9. Hidden pandemic: COVID-19-related stress, SLC6A4 methylation, and infants’ temperament at 3 months
- Author
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Barbara Scelsa, Renato Borgatti, Serena Grumi, Federico Prefumo, Roberto Giorda, Maria Roberta Longo, Giacomo Biasucci, Barbara Gardella, Camilla Pisoni, Livio Provenzi, Marco Villa, Simona Orcesi, Renata Nacinovich, Rossana Falcone, Lidia Decembrino, Andrea Citterio, Fabiana Mambretti, Emanuela Bertazzoli, Provenzi, L, Mambretti, F, Villa, M, Grumi, S, Citterio, A, Bertazzoli, E, Biasucci, G, Decembrino, L, Falcone, R, Gardella, B, Longo, M, Nacinovich, R, Pisoni, C, Prefumo, F, Orcesi, S, Scelsa, B, Giorda, R, and Borgatti, R
- Subjects
Male ,Physiology ,Longitudinal Studie ,0302 clinical medicine ,Pregnancy ,Longitudinal Studies ,Serotonin transporter ,media_common ,Serotonin Plasma Membrane Transport Proteins ,Multidisciplinary ,biology ,05 social sciences ,Methylation ,CpG site ,Prenatal Exposure Delayed Effects ,DNA methylation ,Medicine ,Female ,Serotonin Plasma Membrane Transport Protein ,050104 developmental & child psychology ,Human ,Adult ,Science ,media_common.quotation_subject ,Physiological ,Stress ,Prenatal Exposure Delayed Effect ,Article ,03 medical and health sciences ,Humans ,Infant, Newborn ,SARS-CoV-2 ,COVID-19 ,DNA Methylation ,Pandemics ,Stress, Physiological ,Human behaviour ,medicine ,0501 psychology and cognitive sciences ,Epigenetics ,Pandemic ,business.industry ,Infant ,Paediatrics ,medicine.disease ,Newborn ,Prenatal stress ,biology.protein ,Temperament ,business ,030217 neurology & neurosurgery - Abstract
The COVID-19 pandemic represents a collective trauma that may have enduring stress effects during sensitive periods, such as pregnancy. Prenatal stress may result in epigenetic signatures of stress-related genes (e.g., the serotonin transporter gene, SLC6A4) that may in turn influence infants’ behavioral development. In April 2020, we launched a longitudinal cohort study to assess the behavioral and epigenetic vestiges of COVID-19-related prenatal stress exposure in mothers and infants. COVID-19-related prenatal stress was retrospectively assessed at birth. SLC6A4 methylation was assessed in thirteen CpG sites in mothers and infants’ buccal cells. Infants’ temperament was assessed at 3-month-age. Complete data were available from 108 mother-infant dyads. Greater COVID-19-related prenatal stress was significantly associated with higher infants’ SLC6A4 methylation in seven CpG sites. SLC6A4 methylation at these sites predicted infants’ temperament at 3 months.
- Published
- 2021
10. The hidden pandemic: COVID-19-related stress, SLC6A4 methylation, and infants’ temperament at 3 months
- Author
-
Livio Provenzi, Fabiana Mambretti, Marco Villa, Serena Grumi, Andrea Citterio, Emanuela Bertazzoli, Giacomo Biasucci, Lidia Decembrino, Rossana Falcone, Barbara Gardella, Roberta Longo, Renata Nacinovich, Camilla Pisoni, Federico Prefumo, Simona Orcesi, Barbara Scelsa, Roberto Giorda, Renato Borgatti, Provenzi, L, Mambretti, F, Villa, M, Grumi, S, Citterio, A, Bertazzoli, E, Biasucci, G, Decembrino, L, Falcone, R, Gardella, B, Longo, R, Nacinovich, R, Pisoni, C, Prefumo, F, Orcesi, S, Scelsa, B, Giorda, R, and Borgatti, R
- Subjects
Psychiatry and Mental health ,Endocrinology ,SLC6A4 methylation ,MED/39 - NEUROPSICHIATRIA INFANTILE ,Endocrine and Autonomic Systems ,Endocrinology, Diabetes and Metabolism ,infants’ temperament ,Covid-19 ,Article ,Biological Psychiatry ,prenatal stre - Abstract
Background The COVID-19 pandemic represents a collective trauma that may have enduring stress effects during sensitive periods, such as pregnancy. Prenatal stress may result in epigenetic signatures of stress-related genes (e.g., the serotonin transporter gene, SLC6A4) that may in turn influence infants’ behavioral development. Methods In April 2020, we launched a longitudinal cohort study to assess the behavioral and epigenetic vestiges of COVID-19-related prenatal stress exposure in mothers and infants. COVID-19-related prenatal stress was retrospectively assessed at birth. SLC6A4 methylation was assessed in infants’ buccal cells. Infants’ temperament was assessed at 3-month-age. Results Complete data were available from 108 mother-infant dyads. Greater COVID-19-related prenatal stress was significantly associated with higher infants’ SLC6A4 methylation (RR =.07, p =.007, B =.16 [.05;.29]). SLC6A4 methylation at these sites predicted infants’ temperament at 3 months (RR =.05, p =.027, B = -.45 [-.92;-.06]). Conclusion Indirect effects of the pandemic may alter the trajectories of behavioral development infants. Appropriate prevention and care acts need to be adopted by healthcare systems.
- Published
- 2021
11. The <scp>MRX</scp> complex regulates Exo1 resection activity by altering <scp>DNA</scp> end structure
- Author
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Maria Pia Longhese, Patrick Sung, Corinne Cassani, Elisa Gobbini, Fabiana Mambretti, Weibin Wang, Erika Casari, Giuseppe Zampella, Renata Tisi, Jacopo Vertemara, Gobbini, E, Cassani, C, Vertemara, J, Wang, W, Mambretti, F, Casari, E, Sung, P, Tisi, R, Zampella, G, and Longhese, M
- Subjects
0301 basic medicine ,Saccharomyces cerevisiae Proteins ,genetic processes ,Mutant ,Saccharomyces cerevisiae ,Biology ,Exo1 ,MRX ,General Biochemistry, Genetics and Molecular Biology ,Resection ,03 medical and health sciences ,chemistry.chemical_compound ,Protein Domains ,DNA Breaks, Double-Stranded ,resection ,DNA, Fungal ,Sae2 ,Molecular Biology ,Nuclease ,Endodeoxyribonucleases ,General Immunology and Microbiology ,General Neuroscience ,fungi ,Articles ,double‐strand break ,Cell biology ,enzymes and coenzymes (carbohydrates) ,Exodeoxyribonucleases ,030104 developmental biology ,MRX complex ,chemistry ,Multiprotein Complexes ,health occupations ,biology.protein ,biological phenomena, cell phenomena, and immunity ,Homologous recombination ,Function (biology) ,DNA - Abstract
Homologous recombination is triggered by nucleolytic degradation (resection) of DNA double‐strand breaks (DSBs). DSB resection requires the Mre11‐Rad50‐Xrs2 (MRX) complex, which promotes the activity of Exo1 nuclease through a poorly understood mechanism. Here, we describe the Mre11‐R10T mutant variant that accelerates DSB resection compared to wild‐type Mre11 by potentiating Exo1‐mediated processing. This increased Exo1 resection activity leads to a decreased association of the Ku complex to DSBs and an enhanced DSB resection in G1, indicating that Exo1 has a direct function in preventing Ku association with DSBs. Molecular dynamics simulations show that rotation of the Mre11 capping domains is able to induce unwinding of double‐strand DNA (dsDNA). The R10T substitution causes altered orientation of the Mre11 capping domain that leads to persistent melting of the dsDNA end. We propose that MRX creates a specific DNA end structure that promotes Exo1 resection activity by facilitating the persistence of this nuclease on the DSB ends, uncovering a novel MRX function in DSB resection.
- Published
- 2018
12. Synthetic eco-evolutionary dynamics in simple molecular environment.
- Author
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Casiraghi L, Mambretti F, Tovo A, Paraboschi EM, Suweis S, and Bellini T
- Subjects
- Exercise, Hybridization, Genetic, Oligonucleotides, DNA, Single-Stranded
- Abstract
The understanding of eco-evolutionary dynamics, and in particular the mechanism of coexistence of species, is still fragmentary and in need of test bench model systems. To this aim we developed a variant of SELEX in vitro selection to study the evolution of a population of ∼10
15 single-strand DNA oligonucleotide 'individuals'. We begin with a seed of random sequences which we select via affinity capture from ∼1012 DNA oligomers of fixed sequence ('resources') over which they compete. At each cycle ('generation'), the ecosystem is replenished via PCR amplification of survivors. Massive parallel sequencing indicates that across generations the variety of sequences ('species') drastically decreases, while some of them become populous and dominate the ecosystem. The simplicity of our approach, in which survival is granted by hybridization, enables a quantitative investigation of fitness through a statistical analysis of binding energies. We find that the strength of individual resource binding dominates the selection in the first generations, while inter- and intra-individual interactions become important in later stages, in parallel with the emergence of prototypical forms of mutualism and parasitism., Competing Interests: LC, FM, AT, EP, SS, TB No competing interests declared, (© 2023, Casiraghi, Mambretti et al.)- Published
- 2024
- Full Text
- View/download PDF
13. Maternal and infant NR3C1 and SLC6A4 epigenetic signatures of the COVID-19 pandemic lockdown: when timing matters.
- Author
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Nazzari S, Grumi S, Mambretti F, Villa M, Giorda R, and Provenzi L
- Subjects
- Child, Communicable Disease Control, Female, Humans, Infant, Mouth Mucosa metabolism, Pandemics prevention & control, Pregnancy, COVID-19 epidemiology, COVID-19 prevention & control, Epigenesis, Genetic genetics, Quarantine psychology, Receptors, Glucocorticoid genetics, Receptors, Glucocorticoid metabolism, Serotonin Plasma Membrane Transport Proteins genetics, Serotonin Plasma Membrane Transport Proteins metabolism
- Abstract
Stress exposure during pregnancy is critically linked with maternal mental health and child development. The effects might involve altered patterns of DNA methylation in specific stress-related genes (i.e., glucocorticoid receptor gene, NR3C1, and serotonin transporter gene, SLC6A4) and might be moderated by the gestational timing of stress exposure. In this study, we report on NR3C1 and SLC6A4 methylation status in Italian mothers and infants who were exposed to the COVID-19 pandemic lockdown during different trimesters of pregnancy. From May 2020 to February 2021, 283 mother-infant dyads were enrolled at delivery. Within 24 h from delivery, buccal cells were collected to assess NR3C1 (44 CpG sites) and SLC6A4 (13 CpG sites) methylation status. Principal component (PC) analyses were used to reduce methylation data dimension to one PC per maternal and infant gene methylation. Mother-infant dyads were split into three groups based on the pregnancy trimester (first, second, third), during which they were exposed to the COVID-19 lockdown. Mothers and infants who were exposed to the lockdown during the first trimester of pregnancy had lower NR3C1 and SLC6A4 methylation when compared to counterparts exposed during the second or third trimesters. The effect remained significant after controlling for confounders. Women who were pregnant during the pandemic and their infants might present altered epigenetic biomarkers of stress-related genes. As these epigenetic marks have been previously linked with a heightened risk of maternal psychiatric problems and less-than-optimal child development, mothers and infants should be adequately monitored for psychological health during and after the pandemic., (© 2022. The Author(s).)
- Published
- 2022
- Full Text
- View/download PDF
14. Is Brain-Derived Neurotropic Factor Methylation Involved in the Association Between Prenatal Stress and Maternal Postnatal Anxiety During the COVID-19 Pandemic?
- Author
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Provenzi L, Villa M, Mambretti F, Citterio A, Grumi S, Bertazzoli E, Biasucci G, Decembrino L, Gardella B, Giacchero R, Magnani ML, Nacinovich R, Pisoni C, Prefumo F, Orcesi S, Scelsa B, Giorda R, and Borgatti R
- Abstract
Background: The COVID-19 pandemic is a collective trauma that may expose susceptible individuals to high levels of stress. Pregnant women represent a high-risk population, considering that pregnancy is a period of heightened neuroplasticity and susceptibility to stress through epigenetic mechanisms. Previous studies showed that the methylation status of the BDNF gene is linked with prenatal stress exposure. The goals of this study were (a) to assess the association between pandemic-related stress and postnatal anxiety and (b) to investigate the potential role of maternal BDNF methylation as a significant mediator of this association., Methods: In the present study, we report data on the association among pandemic-related stress during pregnancy, maternal BDNF methylation, and postnatal anxiety symptoms. Pandemic-related stress and postnatal anxiety were assessed through self-report instruments. BDNF methylation was estimated in 11 CpG sites in DNA from mothers' buccal cells. Complete data were available from 108 mothers., Results: Results showed that pandemic-related stress was associated with an increased risk of postnatal anxiety, r = 0.20, p < 0.05. CpG-specific BDNF methylation was significantly associated with both prenatal pandemic-related stress, r = 0.21, p < 0.05, and postnatal maternal anxious symptoms, r = 0.25, p = 0.01. Moreover, a complete mediation by the BDNF CpG6 methylation emerged between pandemic-related stress during pregnancy and postnatal maternal anxiety, ACME = 0.66, p < 0.05., Conclusion: These findings suggest that BDNF epigenetic regulation by pandemic-related stress might contribute to increase the risk of anxiety in mothers. Policymakers should prioritize the promotion of health and wellbeing in pregnant women and mothers during the present healthcare emergency., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Provenzi, Villa, Mambretti, Citterio, Grumi, Bertazzoli, Biasucci, Decembrino, Gardella, Giacchero, Magnani, Nacinovich, Pisoni, Prefumo, Orcesi, Scelsa, Giorda and Borgatti.)
- Published
- 2022
- Full Text
- View/download PDF
15. OxDNA to Study Species Interactions.
- Author
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Mambretti F, Pedrani N, Casiraghi L, Paraboschi EM, Bellini T, and Suweis S
- Abstract
Molecular ecology uses molecular genetic data to answer traditional ecological questions in biogeography and biodiversity, among others. Several ecological principles, such as the niche hypothesis and the competitive exclusions , are based on the fact that species compete for resources. More in generally, it is now recognized that species interactions play a crucial role in determining the coexistence and abundance of species. However, experimentally controllable platforms, which allow us to study and measure competitions among species, are rare and difficult to implement. In this work, we suggest exploiting a Molecular Dynamics coarse-grained model to study interactions among single strands of DNA, representing individuals of different species, which compete for binding to other oligomers considered as resources. In particular, the well-established knowledge of DNA-DNA interactions at the nanoscale allows us to test the hypothesis that the maximum consecutive overlap between pairs of oligomers measure the species' competitive advantages. However, we suggest that a more complex structure also plays a role in the ability of the species to successfully bind to the target resource oligomer. We complement the simulations with experiments on populations of DNA strands which qualitatively confirm our hypotheses. These tools constitute a promising starting point for further developments concerning the study of controlled, DNA-based, artificial ecosystems.
- Published
- 2022
- Full Text
- View/download PDF
16. Hidden pandemic: COVID-19-related stress, SLC6A4 methylation, and infants' temperament at 3 months.
- Author
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Provenzi L, Mambretti F, Villa M, Grumi S, Citterio A, Bertazzoli E, Biasucci G, Decembrino L, Falcone R, Gardella B, Longo MR, Nacinovich R, Pisoni C, Prefumo F, Orcesi S, Scelsa B, Giorda R, and Borgatti R
- Subjects
- Adult, Female, Humans, Infant, Newborn, Longitudinal Studies, Male, Pregnancy, COVID-19 epidemiology, COVID-19 genetics, COVID-19 metabolism, DNA Methylation, Pandemics, Prenatal Exposure Delayed Effects epidemiology, Prenatal Exposure Delayed Effects genetics, Prenatal Exposure Delayed Effects metabolism, SARS-CoV-2 metabolism, Serotonin Plasma Membrane Transport Proteins genetics, Serotonin Plasma Membrane Transport Proteins metabolism, Stress, Physiological
- Abstract
The COVID-19 pandemic represents a collective trauma that may have enduring stress effects during sensitive periods, such as pregnancy. Prenatal stress may result in epigenetic signatures of stress-related genes (e.g., the serotonin transporter gene, SLC6A4) that may in turn influence infants' behavioral development. In April 2020, we launched a longitudinal cohort study to assess the behavioral and epigenetic vestiges of COVID-19-related prenatal stress exposure in mothers and infants. COVID-19-related prenatal stress was retrospectively assessed at birth. SLC6A4 methylation was assessed in thirteen CpG sites in mothers and infants' buccal cells. Infants' temperament was assessed at 3-month-age. Complete data were available from 108 mother-infant dyads. Greater COVID-19-related prenatal stress was significantly associated with higher infants' SLC6A4 methylation in seven CpG sites. SLC6A4 methylation at these sites predicted infants' temperament at 3 months., (© 2021. The Author(s).)
- Published
- 2021
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17. The MRX complex regulates Exo1 resection activity by altering DNA end structure.
- Author
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Gobbini E, Cassani C, Vertemara J, Wang W, Mambretti F, Casari E, Sung P, Tisi R, Zampella G, and Longhese MP
- Subjects
- DNA, Fungal genetics, Endodeoxyribonucleases genetics, Endodeoxyribonucleases metabolism, Exodeoxyribonucleases genetics, Multiprotein Complexes genetics, Protein Domains, Saccharomyces cerevisiae genetics, Saccharomyces cerevisiae Proteins genetics, Saccharomyces cerevisiae Proteins metabolism, DNA Breaks, Double-Stranded, DNA, Fungal metabolism, Exodeoxyribonucleases metabolism, Multiprotein Complexes metabolism, Saccharomyces cerevisiae metabolism
- Abstract
Homologous recombination is triggered by nucleolytic degradation (resection) of DNA double-strand breaks (DSBs). DSB resection requires the Mre11-Rad50-Xrs2 (MRX) complex, which promotes the activity of Exo1 nuclease through a poorly understood mechanism. Here, we describe the Mre11-R10T mutant variant that accelerates DSB resection compared to wild-type Mre11 by potentiating Exo1-mediated processing. This increased Exo1 resection activity leads to a decreased association of the Ku complex to DSBs and an enhanced DSB resection in G1, indicating that Exo1 has a direct function in preventing Ku association with DSBs. Molecular dynamics simulations show that rotation of the Mre11 capping domains is able to induce unwinding of double-strand DNA (dsDNA). The R10T substitution causes altered orientation of the Mre11 capping domain that leads to persistent melting of the dsDNA end. We propose that MRX creates a specific DNA end structure that promotes Exo1 resection activity by facilitating the persistence of this nuclease on the DSB ends, uncovering a novel MRX function in DSB resection., (© 2018 The Authors.)
- Published
- 2018
- Full Text
- View/download PDF
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