Evaluating the role of social attention in the causal path to Autism Spectrum Disorder

This thesis evaluated the evidence for the hypothesis that early disruptions in social attention are involved in the causal pathway to Autism Spectrum Disorder (ASD). The sample included infants at high and low familial risk for neurodevelopmental disorders participating in a prospective longitudinal study, and their family members. Five studies were conducted to test whether social attention atypicalities precede the onset of behavioural symptoms and whether they are related to familial, genetic and epigenetic burden for ASD. Chapter 2 examined neural correlates of attention measured with multi-channel electroencephalography in 8-month-old infants attending to faces and non-social stimuli, in relation to outcomes at age 3. Chapter 3 used structural equation modelling to investigate whether disruptions in neural response have cascading effects on learning from the environment via looking behaviour. Next, to further understand whether disruptions in social attention lie between genetic risk and ASD phenotype, Chapter 4 examined the association between ability to detect eye-gaze direction in a familial sample, severity of ASD symptoms and polygenic risk for ASD. Chapter 5 explored these patterns earlier in development, looking at the relationship between social attention at 14 months of age and familial burden, polygenic risk and parentreport traits of ASD and ADHD. Finally, Chapter 6, leveraging DNA methylation data, explored whether epigenetic signals were associated with early neural and behavioural correlates of social attention as well as developmental change leading to atypical outcome. Taken together, this work examined in depth the multifaceted nature of social attention, pointing to neural and behavioural atypicalities at critical time points as promising targets for cognitive and affective interventions. Furthermore, it pioneers future work integrating genetics, epigenetics and early neurocognitive measures of social attention in large prospective longitudinal studies of individuals at increased vulnerability for neurodevelopmental disorders, to shed light on the developmental mechanisms underlying the emergence of ASD

Evaluating the role of social attention in the causal path to Autism Spectrum Disorder

This thesis evaluated the evidence for the hypothesis that early disruptions in social attention are involved in the causal pathway to Autism Spectrum Disorder (ASD). The sample included infants at high and low familial risk for neurodevelopmental disorders participating in a prospective longitudinal study, and their family members. Five studies were conducted to test whether social attention atypicalities precede the onset of behavioural symptoms and whether they are related to familial, genetic and epigenetic burden for ASD. Chapter 2 examined neural correlates of attention measured with multi-channel electroencephalography in 8-month-old infants attending to faces and non-social stimuli, in relation to outcomes at age 3. Chapter 3 used structural equation modelling to investigate whether disruptions in neural response have cascading effects on learning from the environment via looking behaviour. Next, to further understand whether disruptions in social attention lie between genetic risk and ASD phenotype, Chapter 4 examined the association between ability to detect eye-gaze direction in a familial sample, severity of ASD symptoms and polygenic risk for ASD. Chapter 5 explored these patterns earlier in development, looking at the relationship between social attention at 14 months of age and familial burden, polygenic risk and parentreport traits of ASD and ADHD. Finally, Chapter 6, leveraging DNA methylation data, explored whether epigenetic signals were associated with early neural and behavioural correlates of social attention as well as developmental change leading to atypical outcome. Taken together, this work examined in depth the multifaceted nature of social attention, pointing to neural and behavioural atypicalities at critical time points as promising targets for cognitive and affective interventions. Furthermore, it pioneers future work integrating genetics, epigenetics and early neurocognitive measures of social attention in large prospective longitudinal studies of individuals at increased vulnerability for neurodevelopmental disorders, to shed light on the developmental mechanisms underlying the emergence of ASD

The influence of carbon nanotubes on the combustion toxicity of PP/intumescent flame retardant composites

In recent years, carbon nanotubes (CNTs) have emerged as a promising candidate for improving the flame retardancy of polymer materials, as well as other physical properties. However, few researches have been focused on the influence of this nanoscale material on the combustion toxicity of polymer composites during combustion. In this work, the fire toxicity of polypropylene (PP) composites with intumescent flame retardants (IFRs) and CNTs has been investigated by a Purser Furnace apparatus, which is called steady state tube furnace (SSTF) and enables different fire stages to be created. The Thermo gravimetric analyzer (TGA) and derivative thermo gravimetric analysis (DTG) data indicate that the thermal stability of PP composites was increased by the addition of IFRs or CNTs. However, the SSTF results show that PP samples with IFR or CNTs or both, produced much more carbon monoxide (CO) compared to neat PP during all fire stages, resulting in a much lower CO2/CO ratio. Furthermore, an interesting finding is that the effect of CNTs on the smoke production and CxHy yield of the PP samples during the combustion changes with the combustion equivalence ratio. It indicates that the presence of CNTs promote the formation of smoke particulates from hydrocarbon, but this effect only exist when oxygen supply is not adequate. It is also concluded that the air ventilation and combustion temperature play significant roles in the fire effluent production of PP samples and the morphology of soot particulates

Face processing in early development: a systematic review of behavioral studies and considerations in times of COVID-19 pandemic

Human faces are one of the most prominent stimuli in the visual environment of young infants and convey critical information for the development of social cognition. During the COVID-19 pandemic, mask wearing has become a common practice outside the home environment. With masks covering nose and mouth regions, the facial cues available to the infant are impoverished. The impact of these changes on development is unknown but is critical to debates around mask mandates in early childhood settings. As infants grow, they increasingly interact with a broader range of familiar and unfamiliar people outside the home; in these settings, mask wearing could possibly influence social development. In order to generate hypotheses about the effects of mask wearing on infant social development, in the present work, we systematically review N = 129 studies selected based on the most recent PRISMA guidelines providing a state-of-the-art framework of behavioral studies investigating face processing in early infancy. We focused on identifying sensitive periods during which being exposed to specific facial features or to the entire face configuration has been found to be important for the development of perceptive and socio-communicative skills. For perceptive skills, infants gradually learn to analyze the eyes or the gaze direction within the context of the entire face configuration. This contributes to identity recognition as well as emotional expression discrimination. For socio- communicative skills, direct gaze and emotional facial expressions are crucial for attention engagement while eye-gaze cuing is important for joint attention. Moreover, attention to the mouth is particularly relevant for speech learning. We discuss possible implications of the exposure to masked faces for developmental needs and functions. Providing groundwork for further research, we encourage the investigation of the consequences of mask wearing for infants’ perceptive and socio-communicative development, suggesting new directions within the research field

An Essential Role of N-Terminal Arginylation in Cardiovascular Development

The enzymatic conjugation of arginine to the N-termini of proteins is a part of the ubiquitin-dependent N-end rule pathway of protein degradation. In mammals, three N-terminal residues—aspartate, glutamate, and cysteine—are substrates for arginylation. The mouseATE1 gene encodes a family of Arg-tRNA-protein transferases (R-transferases) that mediate N-terminal arginylation. We constructed ATE1-lacking mouse strains and found thatATE1 −/− embryos die with defects in heart development and in angiogenic remodeling of the early vascular plexus. Through biochemical analyses, we show that N-terminal cysteine, in contrast to N-terminal aspartate and glutamate, is oxidized before its arginylation by R-transferase, suggesting that the arginylation branch of the N-end rule pathway functions as an oxygen sensor

Children’s total blindness as a risk factor for early parent-child relationships: preliminary findings from an Italian sample

BackgroundVision provides crucial information for parent-child attunement that scaffolds social development from the first months of life. Congenital blindness might affect both parental wellbeing and children’s behavior during parent-child interaction. In this study, we compared families of young children with total versus partial blindness to understand the link between residual vision, parenting stress and perceived social support, and children’s behavior during parent-child interaction.MethodsParticipants were 42 white parents (21 fathers and 21 mothers) and their congenitally blind children (14 females, mean age = 14.81 months, SD = 10.46) with no co-occurring disability, recruited at the Robert Hollman Foundation rehabilitation centers in Italy. Parents’ scores on the Parenting Stress Index and Multidimensional Scale of Perceived Social Support questionnaires, as well as children’s behaviors signaling joint engagement during video-recorded episodes of parent-child interaction, were compared between the Total Blindness (TB, n = 12 children with no light perception or light perception in the dark but no quantifiable visual acuity) and Partial Blindness (PB, n = 9 children with a residual visual acuity below 3/60) groups.ResultsWe found that parents of TB children had higher parenting stress and lower perceived social support scores than parents of PB children. In fathers, total stress and stress linked to perceiving the child as difficult negatively correlated with perceived support from friends. There was no difference in the time TB and PB children spent displaying joint engagement behaviors during parent-child interaction. However, TB children directed their gaze and face less often toward their parents than PB children. We observed a trend of association between this behavior and maternal stress.ConclusionThese preliminary results suggest that the complete absence of vision from birth has adverse effects on stress linked to parenting and parental perceived social support. These findings support the importance of early family-centered interventions that extend to the parents’ communities and facilitate the parent-child dyad’s communication through non-visual behaviors. Replication is warranted in larger and more diverse samples

Finding New Cell Wall Regulatory Genes in Populus trichocarpa Using Multiple Lines of Evidence.

Understanding the regulatory network controlling cell wall biosynthesis is of great interest in Populus trichocarpa, both because of its status as a model woody perennial and its importance for lignocellulosic products. We searched for genes with putatively unknown roles in regulating cell wall biosynthesis using an extended network-based Lines of Evidence (LOE) pipeline to combine multiple omics data sets in P. trichocarpa, including gene coexpression, gene comethylation, population level pairwise SNP correlations, and two distinct SNP-metabolite Genome Wide Association Study (GWAS) layers. By incorporating validation, ranking, and filtering approaches we produced a list of nine high priority gene candidates for involvement in the regulation of cell wall biosynthesis. We subsequently performed a detailed investigation of candidate gene GROWTH-REGULATING FACTOR 9 (PtGRF9). To investigate the role of PtGRF9 in regulating cell wall biosynthesis, we assessed the genome-wide connections of PtGRF9 and a paralog across data layers with functional enrichment analyses, predictive transcription factor binding site analysis, and an independent comparison to eQTN data. Our findings indicate that PtGRF9 likely affects the cell wall by directly repressing genes involved in cell wall biosynthesis, such as PtCCoAOMT and PtMYB.41, and indirectly by regulating homeobox genes. Furthermore, evidence suggests that PtGRF9 paralogs may act as transcriptional co-regulators that direct the global energy usage of the plant. Using our extended pipeline, we show multiple lines of evidence implicating the involvement of these genes in cell wall regulatory functions and demonstrate the value of this method for prioritizing candidate genes for experimental validation

Dual Antibiotic Therapy with Vancomycin and Cefazolin for Surgical Prophylaxis in Total Knee Arthroplasty

Background: Perioperative administration of intravenous antibiotics is a routine part of total knee arthroplasty.  Antibiotic selection is a matter of controversy, and the potential risks and benefits associated with each antibiotic selection need to be considered.  The objective of this study is to examine the effects of routine dual antibiotic prophylaxis with both cefazolin and vancomycin on infection and renal failure after primary total knee arthroplasty (TKA) compared with cefazolin alone. Methods: We performed a retrospective review of primary TKA patients for two years before and two years after routine dual antibiotic prophylaxis was implemented at our institution. 1502 patients were included (567 cefazolin-only and 935 dual prophylaxis).   Results: 2 patients (0.4%) in the cefazolin-only group had a deep surgical site infection, compared with 13 patients (1.4%) in the dual prophylaxis group (p=0.06). 46 patients (8.1%) in the cefazolin-only group had postoperative renal failure, compared with 36 patients (3.9%) in the dual prophylaxis group (p=0.0006). Discussion and Conclusion: Our results did not support the routine use of vancomycin in primary total joint arthroplasty to decrease periprosthetic joint infection. However, we also did not see any clear harm due to renal failure in the routine use of dual antibiotic prophylaxis