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The most common causes of congenital myasthenic syndromes (CMS) are CHRNE mutations, and some pathogenic allelic variants in this gene are especially frequent in certain ethnic groups. In the southern region of Brazil, a study found the c.130dupG CHRNE mutation in up to 33% of families with CMS. Here, we aimed to verify the frequency of this mutation among individuals with CMS in a larger cohort of CMS patients from different areas of Brazil and to characterize clinical features of these patients. Eighty-four patients with CMS, from 72 families, were clinically evaluated and submitted to direct sequencing of the exon 2 of CHRNE. The c.130dupG mutation was found in 32 patients (23 families), with 26 patients (19 families, 26.3%) in homozygosis, confirming its high prevalence in different regions of Brazil. Among the homozygous patients, the following characteristics were frequent: onset of symptoms before 2 years of age (92.3%), little functional restriction (92.3%), fluctuating symptoms (100%), ocular muscle impairment (96.1%), ptosis (100%), limb weakness (88.4%), response to pyridostigmine (100%), facial involvement (77%), and bulbar symptoms (70.8%). The pretest probability of finding at least one allele harbouring the c.130dupG mutation was 38.1%. Selecting only patients with impaired eye movement together with limb weakness and improvement with pyridostigmine, the probability increases to 72.2%. This clinical pre-selection of patients is likely a useful tool for regions where CHRNE mutations have a founder effect. In conclusion, the CHRNE mutation c.130dupG leads to fairly benign natural course of the disease with relative homogeneity.

The circular economy (CE) has become a trend because concern has arisen regarding the end of life of several products and the reduction of CO2 emissions in many processes. Since the architecture, engineering, and construction (AEC) industry is one of the biggest generators of environmental impacts, there is a need to apply the CE concept to the industry in order to reduce greenhouse gas (GHG) emissions. However, the role of different tools that are used to integrate CE strategies to reduce GHG emissions by the AEC industry is still unknown in the scientific literature. The purpose of this paper is to carry out a systematic literature review on the theme and analyze the following seven tools: (1) life cycle assessment—LCA; (2) building information modeling—BIM; (3) building environmental certifications—BEC; (4) building materials passports—BMP; (5) waste management plan—WMP; (6) augmented reality—AR; and (7) virtual reality—VR. A total of 30 papers were reviewed, and it was observed that, in terms of CE strategies and climate change mitigation, the vast majority can be classified as closing loops and are mainly related to recycling and reuse at the end of life and the use of recycled materials. Considering the building’s stakeholders, constructors, researchers, and designers can be the main users and, consequently, those that most benefit from the use of the evaluated tools. The integration between LCA, BIM, and BMP was also observed. Finally, as one of the main contributions of this research, other types of integration among the analyzed tools are proposed. These proposals seek to improve and update the tools and also address the need to reduce GHG emissions.

The SARS-CoV-2 nucleocapsid protein (N) is a multifunctional promiscuous nucleic acid-binding protein, which plays a major role in nucleocapsid assembly and discontinuous RNA transcription, facilitating the template switch of transcriptional regulatory sequences (TRS). Here, we dissect the structural features of the N protein N-terminal domain (N-NTD), either with or without the SR-rich motif (SR), upon binding to single and double-stranded TRS DNA, as well as their activities for dsTRS melting and TRS-induced liquid-liquid phase separation (LLPS). Our study gives insights on specificity for N-NTD/N-NTD-SR interaction with TRS, including an unfavorable energetic contribution to binding along with hydrogen bonds between the triple-thymidine (TTT) motif in the dsTRS and β-sheet II due to the defined position and orientation of the DNA duplex, a well-defined pattern (ΔH > 0 and ΔS > 0 for ssTRS, and ΔH < 0 and ΔS < 0 for dsTRS) for the thermodynamic profile of binding, and a preference for TRS in the formation of liquid condensates when compared to a non-specific sequence. Moreover, our results on DNA binding may serve as a starting point for the design of inhibitors, including aptamers, against N, a possible therapeutic target essential for the virus infectivity. Competing Interest Statement The authors have declared no competing interest.