The Upper Precambrian of South America

This paper deals with the structural organization and tectonic evolution of South American Continent basement during the Upper Precambrian. The South American Platform is the old platform of South America. It has more than half of this extension covered by sediments and volcanic rocks of Phanerozoic age; the basement is exposed in three vast shields and several little massifs. In the exposed basement some cratonic nuclei have been distinguished, with structures developed in the Middle Precambrian (Trans-Amazonic) and Lower Precambrian (Jequié and Guriense). The Lower Precambrian structures are described in small scattered nuclei, all the rest seeming to have been remobilized by tectonic, magmatic and thermal processes of Trans-Amazonic age. These processes affected large areas but are still insufficiently understood. In the Upper Precambrian, these cratonic nuclei underwent intense process of reactivation, in large areas, with formation of volcano-sedimentary covers, acid, basic and alkaline intrusive rocks, cataclastic zones and thermally affected zones. During the Upper Precambrian, geosynclinal evolution processes developed at the borders and between the cratons, generating fold belts and regions. The firstly developed belt is located in Central Brazil, related to the Uruaçuano Cycle (ca. 1300-1000 m.a.). The Espinhaço and Uruaçu Belts are attributed to this cycle. The other units are related to the Brasiliano Cycle ( 1000 m.y. to Cambro-Ordovician time). The fold belts are located in marginal position and the fold regions are between cratonic areas: both show different characteristic of organization, sedimentation, structures, tectonism, metamorphism, magmatism and metallogenesis. In the southern border of the South American Platform a fold region developed, which possibly represents the extension of the Southeastern Fold Region, and continues to the Andean Belt. The South American Platform consolidated during Cambro-Ordovician time. Its western and southern adjacent areas were places of geosynclinal evolution up to the Devonian in the Patagonian Platform and up to the Cenozoic in the Andean Chain. The eastern half of the South American Platform had a platformal evolution since the Siluria

PYROMEMS IGNITER BASED ON A TEMPERATURE GRADIENT: CONCEPT, FABRICATION AND CHARACTERIZATION

A pyroMEMS igniter with increased combustion reliability is presented. The igniter consisted of a thin-film platinum Joule heater fabricated on a borosilicate glass substrate. Two different igniter layouts (meandering and annular) and three different binder mass fractions (5, 10 and 20 %) were evaluated. High-speed videos were used to judge the success or failure of the combustion events. Although the ignition success rate was 100 %, the combustion success rate was approximately 87.5 ± 7.1 % for the annular design versus 12.5 ± 7.1 % for the meandering layout. No effect on success rate was observed for the different binder contents tested. Rather, increasing the binder mass fraction increased the combustion duration

Genetic and phenotypic spectrum associated with IFIH1 gain-of-function

IFIH1 gain‐of‐function has been reported as a cause of a type I interferonopathy encompassing a spectrum of autoinflammatory phenotypes including Aicardi–Goutières syndrome and Singleton Merten syndrome. Ascertaining patients through a European and North American collaboration, we set out to describe the molecular, clinical and interferon status of a cohort of individuals with pathogenic heterozygous mutations in IFIH1. We identified 74 individuals from 51 families segregating a total of 27 likely pathogenic mutations in IFIH1. Ten adult individuals, 13.5% of all mutation carriers, were clinically asymptomatic (with seven of these aged over 50 years). All mutations were associated with enhanced type I interferon signaling, including six variants (22%) which were predicted as benign according to multiple in silico pathogenicity programs. The identified mutations cluster close to the ATP binding region of the protein. These data confirm variable expression and nonpenetrance as important characteristics of the IFIH1 genotype, a consistent association with enhanced type I interferon signaling, and a common mutational mechanism involving increased RNA binding affinity or decreased efficiency of ATP hydrolysis and filament disassembly rate

Stress granules, RNA-binding proteins and polyglutamine diseases: too much aggregation?

Stress granules (SGs) are membraneless cell compartments formed in response to different stress stimuli, wherein translation factors, mRNAs, RNA-binding proteins (RBPs) and other proteins coalesce together. SGs assembly is crucial for cell survival, since SGs are implicated in the regulation of translation, mRNA storage and stabilization and cell signalling, during stress. One defining feature of SGs is their dynamism, as they are quickly assembled upon stress and then rapidly dispersed after the stress source is no longer present. Recently, SGs dynamics, their components and their functions have begun to be studied in the context of human diseases. Interestingly, the regulated protein self-assembly that mediates SG formation contrasts with the pathological protein aggregation that is a feature of several neurodegenerative diseases. In particular, aberrant protein coalescence is a key feature of polyglutamine (PolyQ) diseases, a group of nine disorders that are caused by an abnormal expansion of PolyQ tract-bearing proteins, which increases the propensity of those proteins to aggregate. Available data concerning the abnormal properties of the mutant PolyQ disease-causing proteins and their involvement in stress response dysregulation strongly suggests an important role for SGs in the pathogenesis of PolyQ disorders. This review aims at discussing the evidence supporting the existence of a link between SGs functionality and PolyQ disorders, by focusing on the biology of SGs and on the way it can be altered in a PolyQ disease context.ALG-01-0145-FEDER-29480, SFRH/BD/133192/2017, SFRH/BD/133192/2017, SFRH/BD/148533/2019info:eu-repo/semantics/publishedVersio

Endocrine and Growth Abnormalities in 4H Leukodystrophy Caused by Variants in POLR3A, POLR3B, and POLR1C.

CONTEXT: 4H or POLR3-related leukodystrophy is an autosomal recessive disorder typically characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism, caused by biallelic pathogenic variants in POLR3A, POLR3B, POLR1C, and POLR3K. The endocrine and growth abnormalities associated with this disorder have not been thoroughly investigated to date. OBJECTIVE: To systematically characterize endocrine abnormalities of patients with 4H leukodystrophy. DESIGN: An international cross-sectional study was performed on 150 patients with genetically confirmed 4H leukodystrophy between 2015 and 2016. Endocrine and growth abnormalities were evaluated, and neurological and other non-neurological features were reviewed. Potential genotype/phenotype associations were also investigated. SETTING: This was a multicenter retrospective study using information collected from 3 predominant centers. PATIENTS: A total of 150 patients with 4H leukodystrophy and pathogenic variants in POLR3A, POLR3B, or POLR1C were included. MAIN OUTCOME MEASURES: Variables used to evaluate endocrine and growth abnormalities included pubertal history, hormone levels (estradiol, testosterone, stimulated LH and FSH, stimulated GH, IGF-I, prolactin, ACTH, cortisol, TSH, and T4), and height and head circumference charts. RESULTS: The most common endocrine abnormalities were delayed puberty (57/74; 77% overall, 64% in males, 89% in females) and short stature (57/93; 61%), when evaluated according to physician assessment. Abnormal thyroid function was reported in 22% (13/59) of patients. CONCLUSIONS: Our results confirm pubertal abnormalities and short stature are the most common endocrine features seen in 4H leukodystrophy. However, we noted that endocrine abnormalities are typically underinvestigated in this patient population. A prospective study is required to formulate evidence-based recommendations for management of the endocrine manifestations of this disorder

Qualitative evaluation of a preventive intervention for the offspring of parents with a history of depression

Background: Meta-analyses of randomised controlled trials suggest that psychological interventions to reduce children’s risk of depression are effective. Nevertheless, these effects are modest and diminish over time. The Medical Research Council recommends a mixed-methods approach to the evaluation of complex interventions. By gaining a more thorough understanding of participants’ perspectives, qualitative evaluations of preventive interventions could improve their efficacy, longevity and transfer into clinical practice. Methods: 18 parents and 22 children who had received a 12-session family- and group-based cognitivebehavioural intervention to prevent youth depression as part of a randomised controlled trial took part in semistructured interviews or a focus group about aspects which had been perceived as helpful, elements they were still using after the intervention had ended, and suggestions they had for improving the intervention. Results: The chance to openly share and discuss their experiences of depression within and between families was considered helpful by both children and parents. Children benefitted the most from learning coping strategies for dealing with stress and many still used them in everyday life. Parents profited mostly from increasing positive family time, but noted that maintaining new routines after the end of the intervention proved difficult. Participants were generally content with the intervention but commented on how tiring and time consuming it was. Conclusions: Managing parents’ expectations of family-based interventions in terms of their own mental health needs (versus those of their children) and leaving more room for open discussions may result in interventions which are more appealing to participating families. Increasing intervals between sessions may be one means of improving the longevity of interventions. Trial registration: The original RCT this evaluation is a part of was registered under NCT02115880