A biophysical basis for the emergence of the genetic code in protocells

The origin of the genetic code is an abiding mystery in biology. Hints of a 'code within the codons' suggest biophysical interactions, but these patterns have resisted interpretation. Here, we present a new framework, grounded in the autotrophic growth of protocells from CO2 and H2. Recent work suggests that the universal core of metabolism recapitulates a thermodynamically favoured protometabolism right up to nucleotide synthesis. Considering the genetic code in relation to an extended protometabolism allows us to predict most codon assignments. We show that the first letter of the codon corresponds to the distance from CO2 fixation, with amino acids encoded by the purines (G followed by A) being closest to CO2 fixation. These associations suggest a purine-rich early metabolism with a restricted pool of amino acids. The second position of the anticodon corresponds to the hydrophobicity of the amino acid encoded. We combine multiple measures of hydrophobicity to show that this correlation holds strongly for early amino acids but is weaker for later species. Finally, we demonstrate that redundancy at the third position is not randomly distributed around the code: non-redundant amino acids can be assigned based on size, specifically length. We attribute this to additional stereochemical interactions at the anticodon. These rules imply an iterative expansion of the genetic code over time with codon assignments depending on both distance from CO2 and biophysical interactions between nucleotide sequences and amino acids. In this way the earliest RNA polymers could produce non-random peptide sequences with selectable functions in autotrophic protocells

Carbon nanotubes based multi-directional strain sensor

In this work a new carbon nanotubes (CNT) based multi-directional strain sensor capable of quantifying and indicate strain direction is foreseen. This work investigates the electromechanical behavior of an aligned CNT sensing patch strained at 45◦ in order to validate its multi-directional sensing capability. Vertically aligned CNT forests are produced by chemical vapor deposition (CVD) and then mechanically knocked down onto polyimide (PI) films. Two configurations, diamond (D sample) and square (Sq sample), are considered. The relative electrical resistance (ΔR/R0) and the electrical anisotropy (RB/RA) upon strain increments are analyzed and compared to previous work results (0◦ and 90◦ strain direction). Both 45◦ samples, D and Sq, are sensitive to strain. A correlation between electrical anisotropy behavior and strain direction (0◦, 45◦ and 90◦) is established. The results show that with only an aligned CNT small patch it is possible to quantify and indicate strain in three directions.This work was partially funded under the project “IAMAT – Introduction of advanced materials technologies into new product development for the mobility industries”, with reference MITP-TB/PFM/0005/2013, under the MIT-Portugal program exclusively financed by FCT – Fundação para a Ciência e Tecnologia. This work was also co-financed by national funds through FCT – Fundação para a Ciência e Tecnologia, with the scope of projects with references UIDB/05256/2020 and UIDP/05256/2020”

The cholesterol 24-hydroxylase activates autophagy and decreases mutant huntingtin build-up in a neuroblastoma culture model of Huntington’s disease

Objective Compromised brain cholesterol turnover and altered regulation of brain cholesterol metabolism have been allied with some neurodegenerative diseases, including Huntington’s disease (HD). Following our previous studies in HD, in this study we aim to investigate in vitro in a neuroblastoma cellular model of HD, the effect of CYP46A1 overexpression, an essential enzyme in cholesterol metabolism, on huntingtin aggregation and levels. Results We found that CYP46A1 reduces the quantity and size of mutant huntingtin aggregates in cells, as well as the levels of mutant huntingtin protein. Additionally, our results suggest that the observed beneficial effects of CYP46A1 in HD cells are linked to the activation of autophagy. Taken together, our results further demonstrate that CYP46A1 is a pertinent target to counteract HD progression.This work was supported by Brainvectis and E.rare: E-Rare Joint Transnational Call for Proposals 2017 “Transnational Research Projects for Innovative Therapeutic Approaches for Rare Diseases”. CN laboratory is supported by the French Muscular Dystrophy Association (AFM-Téléthon), the Ataxia UK, and the Fundação para a Ciência e Tecnologia (project ALG-01-0145-FEDER-29480 “SeGrPolyQ”). AM is supported by a Ph.D. fellowship from FCT (SFRH/BD/133192/2017)info:eu-repo/semantics/publishedVersio

Aligned carbon nanotube based sensors for strain sensing applications

This paper presents an aligned carbon nanotube (CNT)-based strain sensor. Vertical aligned carbon nanotubes (VA-CNT), synthesized by chemical vapour deposition (CVD), were knocked down onto polymeric films, in order to obtain a thin 10 × 10 × 0.05 mm CNT patch. Different polymeric substrates, ADEXepoxy, polyethylene terephthalate (PET) and polyimide (PI) were used. The samples’ morphology before and after the knock down process, specifically their alignment, was observed by scanning electron microscopy (SEM). The good quality of the synthesized VA-CNT was assessed by Raman spectroscopy. Furthermore, transmission electron microscopy (TEM) analysis was carried out to determine the average wall number and diameters (inner and outer) of the VA-CNT. A MATLAB software with an adapted Van der Pauw method for anisotropic conductors was developed to determine the electric properties of the obtained samples, which were strained in the transverse (X) and parallel (Y) directions with respect to the CNT alignment. The electric anisotropy, defined as electric resistance ratio between obtained measurements along the X (Rxx) and Y (Ryy) -axes, decreases with deformation increment when the sample was strained in the Y-direction, while it increases when strained in the X-direction. Moreover, the obtained Gauge factor values showed a much sensitive response to deformation, i.e., approximately 47% increase in GF values, when the samples are strained transversely to CNT alignment. These results showed that the piezoresistive CNT/polymeric based sensor produced is suitable for strain sensing applications.This work was funded under the project "IAMAT -Introduction of advanced materials technologies into new product development for the mobility industries", with reference MITP-TB/PFM/0005/2013, under the MIT-Portugal program exclusively financed by FCT - Fundacao para a Ciencia e Tecnologia. This work was carried out in part using the Advanced Electron Microscopy, Imaging and Spectroscopy Facility (TEM) of INL - Iberian Nanotechonology Laboratory

Combining experiments and in silico modeling to infer the role of adhesion and proliferation on the collective dynamics of cells

The collective dynamics of cells on surfaces and interfaces poses technological and theoretical challenges in the study of morphogenesis, tissue engineering, and cancer. Different mechanisms are at play, including, cellâ cell adhesion, cell motility, and proliferation. However, the relative importance of each one is elusive. Here, experiments with a culture of glioblastoma multiforme cells on a substrate are combined with in silico modeling to infer the rate of each mechanism. By parametrizing these rates, the time-dependence of the spatial correlation observed experimentally is reproduced. The obtained results suggest a reduction in cellâ cell adhesion with the density of cells. The reason for such reduction and possible implications for the collective dynamics of cancer cells are discussed.e Portuguese Foundation for Science and Technology (FCT) under Contracts no. PTDC/FIS-MAC/28146/2017 (LISBOA-01-0145-FEDER-028146), UIDB/00618/2020, and UIDP/00618/2020. F.R.M. also acknowledges FCT for her contract under the Transitional Rule DL 57/2016 (CTTI-57/18-I3BS(5)

Genome Sequencing of 10 Helicobacter pylori Pediatric Strains from Patients with Nonulcer Dyspepsia and Peptic Ulcer Disease

We present draft genome sequences of 10 Helicobacter pylori clinical strains isolated from children. This will be important for future studies of comparative genomics in order to better understand the virulence determinants underlying peptic ulcer disease.This work was supported by the FCT-PTDC/BIM-MEC/1051/2012 grant from the Fundação para a Ciência e a Tecnologia (FCT) (to M.O.). A.N. and F.F.V. are recipients of postdoctoral fellowships (SFRH/BPD/75295/2010 and SFRH/BPD/95125/2013, respectively) from FCT, and R.R. is a recipient of a fellowship (BRJ-DDI/2012) from the National Institute of Health

Vigilância da Gripe em Portugal no inverno 2013/2014

Introdução: O Programa Nacional de Vigilância da Gripe tem como objetivos: recolha, análise e divulgação da informação sobre a atividade gripal em Portugal. A vigilância clínica e laboratorial possibilita a determinação semanal das taxas de incidência de síndroma gripal (SG), identificação/ caracterização do vírus influenza, deteção de surtos, vírus emergentes com potencial pandémico e risco para a saúde pública. Foi analisada e descrita a atividade gripal em Portugal, na época de 2013/2014. Materiais e Métodos: Em 2013/2014, colaboraram: a Rede de Médicos-Sentinela (Rede MS), possibilitando o cálculo da taxa de incidência da síndroma gripal. Na componente laboratorial, colaboram Rede MS, Rede de Serviços-Urgência, médicos projeto-EuroEVA e Rede Portuguesa Laboratórios Diagnóstico Gripe com envio de amostras respiratórias para pesquisa/caraterização do vírus influenza. Resultados: Em 2013/2014, a atividade gripal foi moderada. O período epidémico ocorreu entre as semanas 1/2014 e 8/2014, valor máximo 80,7 casos SG / 100000 habitantes na semana 4/2014. A análise laboratorial a 869 exsudados-nasofaringe permitiu a identificação do vírus influenza em 467 (54%) casos de SG. Destes, 460 (98,5%) do tipo A: 279 (32%) do subtipo A(H1)pdm09 e 181 (21%) do subtipo AH3. Foram detetados 7 vírus influenza do tipo B. Discussão e Conclusão: Na época 2013/2014, a atividade gripal foi moderada com taxas de incidência semelhantes às 2012/2013. O período epidémico ocorreu mais cedo em relação a 2012/2013 e foi de menor duração. O vírus influenza do tipo A foi predominante com co-circulação dos dois subtipos: A(H1)pdm09 e A(H3). Os vírus detetados são genética e antigenicamente semelhantes às estirpes vacinais e sensíveis ao oseltamivir e zanamivir

Low-level expression of HER2 and CK19 in normal peripheral blood mononuclear cells: relevance for detection of circulating tumor cells

<p>Abstract</p> <p>Background</p> <p>Detection of circulating tumor cells (CTC) in the blood of cancer patients may have prognostic and predictive significance. However, background expression of 'tumor specific markers' in peripheral blood mononuclear cells (PBMC) may confound these studies. The goal of this study was to identify the origin of Cytokeratin 19 (CK19) and HER-2 signal in PBMC and suggest an approach to enhance techniques involved in detection of CTC in breast cancer patients.</p> <p>Methods</p> <p>PBMC from healthy donors were isolated and fractionated into monocytes, lymphocytes, natural killer cells/granulocytes and epithelial populations using immunomagnetic selection and fluorescent cell-sorting for each cell type. RNA isolated from each fraction was analyzed for CK19, HER2 and Beta 2 microglobulin (B2M) using real-time qRT-PCR. Positive selection for epithelial cells and negative selection for NK/granulocytes were used in an attempt to reduce background expression of CK19 and HER2 markers.</p> <p>Results</p> <p>In normal PBMC, CK19 was expressed in the lymphocyte population while HER-2 expression was highest in the NK/granulocyte population. Immunomagnetic selection for epithelial cells reduced background CK19 signal to a frequency of <5% in normal donors. Using negative selection, the majority (74–98%) of HER2 signal could be removed from PBMC. Positive selection methods are variably effective at reducing these background signals.</p> <p>Conclusion</p> <p>We present a novel method to improve the specificity of the traditional method of detecting CTC by identifying the source of the background signals and reducing them by negative immunoselection. Further studies are warranted to improve sensitivity and specificity of methods of detecting CTC will prove to be useful tools for clinicians in determining prognosis and monitoring treatment responses of breast cancer patients.</p

Impact of susceptibility-induced distortion correction on perfusion imaging by pCASL with a segmented 3D GRASE readout

Purpose: The consensus for the clinical implementation of arterial spin labeling (ASL) perfusion imaging recommends a segmented 3D Gradient and Spin-Echo (GRASE) readout for optimal signal-to-noise-ratio (SNR). The correction of the associated susceptibility-induced geometric distortions has been shown to improve diagnostic precision, but its impact on ASL data has not been systematically assessed and it is not consistently part of pre-processing pipelines. Here, we investigate the effects of susceptibility-induced distortion correction on perfusion imaging by pseudo-continuous ASL (pCASL) with a segmented 3D GRASE readout. Methods: Data acquired from 28 women using pCASL with 3D GRASE at 3T was analyzed using three pre-processing options: without distortion correction, with distortion correction, and with spatial smoothing (without distortion correction) matched to control for blurring effects induced by distortion correction. Maps of temporal SNR (tSNR) and relative perfusion were analyzed in eight regions-of-interest (ROIs) across the brain. Results: Distortion correction significantly affected tSNR and relative perfusion across the brain. Increases in tSNR were like those produced by matched spatial smoothing in most ROIs, indicating that they were likely due to blurring effects. However, that was not the case in the frontal and temporal lobes, where we also found increased relative perfusion with distortion correction even compared with matched spatial smoothing. These effects were found in both controls and patients, with no interactions with the participant group. Conclusion: Correction of susceptibility-induced distortions significantly impacts ASL perfusion imaging using a segmented 3D GRASE readout, and this step should therefore be considered in ASL pre-processing pipelines. This is of special importance in clinical studies, reporting perfusion across ROIs defined on relatively undistorted images and when conducting group analyses requiring the alignment of images across different subjects.info:eu-repo/semantics/publishedVersio