Induced pluripotent stem cells, a giant leap for mankind therapeutic applications

Induced pluripotent stem cells (iPSC) technology has propelled the field of stem cells biology, providing new cells to explore the molecular mechanisms of pluripotency, cancer biology and aging. A major advantage of human iPSC, compared to the pluripotent embryonic stem cells, is that they can be generated from virtually any embryonic or adult somatic cell type without destruction of human blastocysts. In addition, iPSC can be generated from somatic cells harvested from normal individuals or patients, and used as a cellular tool to unravel mechanisms of human development and to model diseases in a manner not possible before. Besides these fundamental aspects of human biology and physiology that are revealed using iPSC or iPSC-derived cells, these cells hold an immense potential for cell-based therapies, and for the discovery of new or personalized pharmacological treatments for many disorders. Here, we review some of the current challenges and concerns about iPSC technology. We introduce the potential held by iPSC for research and development of novel health-related applications. We briefly present the efforts made by the scientific and clinical communities to create the necessary guidelines and regulations to achieve the highest quality standards in the procedures for iPSC generation, characterization and long-term preservation. Finally, we present some of the audacious and pioneer clinical trials in progress with iPSC-derived cells.info:eu-repo/semantics/publishedVersio

A multiparameter family of irreducible representations of the quantum plane and of the quantum Weyl algebra

We construct a family of irreducible representations of the quantum plane and of the quantum Weyl algebra over an arbitrary field, assuming the deformation parameter is not a root of unity. We determine when two representations in this family are isomorphic, and when they are weight representations, in the sense of Bavula.Comment: 12 pages, Section 2 has been reorganized, new material added in a new Section

From Fundamental Strings to Small Black Holes

We give evidence in favour of a string/black hole transition in the case of BPS fundamental string states of the Heterotic string. Our analysis goes beyond the counting of degrees of freedom and considers the evolution of dynamical quantities in the process. As the coupling increases, the string states decrease their size up to the string scale when a small black hole is formed. We compute the absorption cross section for several fields in both the black hole and the perturbative string phases. At zero frequency, these cross sections can be seen as order parameters for the transition. In particular, for the scalars fixed at the horizon the cross section evolves to zero when the black hole is formed.Comment: 36 pages, 4 figures, argument about minimally coupled scalar absorption cross section clarifie

Gestational protein restriction induces CA3 dendritic atrophy in dorsal hippocampal neurons but does not alter learning and memory performance in adult offspring

Studies have demonstrated that nutrient deficiency during pregnancy or in early postnatal life results in structural abnormalities in the offspring hippocampus and in cognitive impairment. In an attempt to analyze whether gestational protein restriction might induce learning and memory impairments associated with structural changes in the hippocampus, we carried out a detailed morphometric analysis of the hippocampus of male adult rats together with the behavioral characterization of these animals in the Morris water maze (MWM). Our results demonstrate that gestational protein restriction leads to a decrease in total basal dendritic length and in the number of intersections of CA3 pyramidal neurons whereas the cytoarchitecture of CA1 and dentate gyrus remained unchanged. Despite presenting significant structural rearrangements, we did not observe impairments in the MWM test. Considering the clear dissociation between the behavioral profile and the hippocampus neuronal changes, the functional significance of dendritic remodeling in fetal processing remains undisclosed

Near-infrared spectroscopy for the detection and quantification of bacterial contaminations in pharmaceutical products

Accurate detection and quantification of microbiological contaminations remains an issue mainly due the lack of rapid and precise analytical techniques. Standard methods are expensive and time-consuming being associated to high economic losses and public health threats. In the context of pharmaceutical industry, the development of fast analytical techniques able to overcome these limitations is crucial and spectroscopic techniques might constitute a reliable alternative. In this work we proved the ability of Fourier transform near infrared spectroscopy (FT-NIRS) to detect and quantify bacteria (Bacillus subtilis, Escherichia coli, Pseudomonas fluorescens, Salmonella enterica, Staphylococcus epidermidis) from 10-108 CFUs/mL in sterile saline solutions (NaCl 0.9%). Partial least squares discriminant analysis (PLSDA) models showed that FT-NIRS was able to discriminate between sterile and contaminated solutions for all bacteria as well as to identify contaminant bacteria. Partial least squares (PLS) models allowed bacterial quantification with limits of detection ranging from 5.1 to 9CFU/mL for E. coli and B. subtilis, respectively. This methodology was successfully validated in three pharmaceutical preparations (contact lens solution, cough syrup and topic anti-inflammatory solution) proving that this technique possess a high potential to be routinely used for the detection and quantification of bacterial contaminations.This work was funded by Fundacao para a Ciencia e a Tecnologia (FCT) under the project UID/QUI/50006/2013. The authors also thank the FCT Strategic Project of UID/BIO/04469/2013 unit, the project RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462) and the project "BioInd-Biotechnology and Bioengineering for improved Industrial and Agro-Food processes", REF. NORTE-07-0124-FEDER-000028 co-funded by the Programa Operacional Regional do Norte (ON. 2-O Novo Norte), QREN, FEDER. Daniela Mesquita (SFRH/BPD/82558/2011) and Cristina Quintelas were funded by post-doctoral grants from FCT and ON.2. Clara Sousa was funded by a CIENCIA2008 contract from FCT

Using coarse-grained molecular dynamics to understand the effect of ionic liquids on the aggregation of Pluronic copolymer solutions

This study is aimed to enhance the understanding of the interaction between ionic liquids (ILs) and non-ionic Pluronic triblock copolymers in aqueous two-phase micellar systems (ATPMS) used for the selective separation/purification of hydrophobic biomolecules. The ILs allow a precise control of the cloud point phase separation temperature (CPT), particularly important when the stability of the molecule is highly dependent on temperature. The effect of choline-based ILs, with two different counter-anions, chloride and hexanoate, was evaluated using molecular dynamics simulations (MD) for F-68 and L-35 Pluronic aqueous solutions. The simulations revealed the role played by the anions during the Pluronic self-assembly, with choline chloride hindering Pluronic aggregation and the choline hexanoate favouring micelle formation and coalescence, in agreement with the experimental data. A detailed study of the accessible surface area of Pluronic showed a progressive dehydration of the Pluronic hydrophilic micelle corona in choline hexanoate mixtures promoting inter-micelle interactions and, consequently, micelle coalescence. With the addition of choline hexanoate, it was observed that the hydrophilic segments, which form the micelle corona, twisted towards the Pluronic micelle core. The electrostatic interaction is also shown to play a key role in this IL–Pluronic aqueous solution, as the hexanoate anions are accommodated in the Pluronic micelle core, while the choline cations are hosted by the Pluronic micelle corona, with the ions interacting with each other during the self-assembly process. In addition, a comparison study of F-68 and L-35 aqueous solutions shows that the IL impact depends on the length of the Pluronic hydrophilic segment. This work provides a realistic microscopic scenario of the complex interactions between Pluronic copolymers and ILs.This work was developed within the scope of the project CICECO-Aveiro Institute of Materials, UIDB/50011/2020 & UIDP/50011/2020, financed by national funds through the FCT/MEC and when appropriate co-financed by FEDER under the PT2020 Partnership Agreement. The authors acknowledge the research contract under the project CENTRO-01-0145- FEDER-000005: SusPhotoSolutions: Soluções Fotovoltaicas Sustentáveis. G. Pérez-Sánchez and N. Schaeffer acknowledge the national funds (OE), through FCT – Fundação para a Ciência e a Tecnologia, I. P., in the scope of the framework contract foreseen in the numbers 4, 5 and 6 of the article 23, of the Decree-Law 57/2016, of August 29th, changed by Law 57/2017, of July 19th. A. M. Lopes acknowledges the support from the State of São Paulo Research Foundation (FAPESP/Brazil, processes #2017/10789-1 and #2018/10799-0). J. F. B. Pereira also acknowledges FAPESP through the project 2014/16424-7.publishe

La(2/3)Sr(1/3)MnO(3) thin films deposited by laser ablation on lithium niobate substrates

The structural, magnetic and transport properties of La(2/3)Sr(1/3)MnO(3) thin films, prepared by laser ablation on LiNbO(3) substrates, have been characterized for different temperatures and applied magnetic fields. The deposited films have grown highly oriented, with a (111) preferred growth direction. Their lattice parameter was a = 3.86 angstrom. From the temperature dependence of the magnetization and of the electrical resistivity their Curie (T(C)) and metal-insulator (T(MI)) transition temperatures were determined (T(C) similar to 360 K, T(MI) similar to 260 K). Spin-dependent tunnelling across grain boundaries was found to dominate the behaviour of the transport properties of the La(2/3)Sr(1/3)MnO(3) thin films, on the studied temperature region.I.T. Gomes gratefully acknowledges a PhD grant from Fundação para a Ciência e Tecnologia (SFRH/BD/36348/2007)

Characterization of phenolic compounds of OMW : toxicity and degradability by yeasts

The characterization of Olive Mill Wastewaters (OMW), focusing the phenolic compounds, is one of the aims of the present work. As a first approach to characterize the phenolic compounds of OMW, the extraction methods used were: a liquid-liquid extraction by acidified ethyl acetate and a solid-liquid extraction with acidified methanol. The analysis of these extracts by reversed phase liquid chromatography confirmed that hydroxytyrosol was the most abundant phenolic compound in OMW, and that this compound was more efficiently recovered by the solid-liquid extraction technique. It was also a goal of this work to study the phenolic compounds toxicity to some yeast strains. Among the phenolic compounds tested catechol is the most inhibitory one to the cells. The phenols degradation was quite difficult, particularly when more easily degradable carbon source is still present in the medium.Fundação para a Ciência e a Tecnologia (FCT) - PTDC/AMB/69379/2006, SFRH/BD/27915/200

Novel insights into biomass delignification with acidic deep eutectic solvents: a mechanistic study of β-O-4 ether bond cleavage and the role of the halide counterion in the catalytic performance

The development of innovative technologies for an efficient, yet eco-friendly, biomass delignification is required to achieve higher sustainability than traditional processes. In this context, the use of deep eutectic solvents (DES) for the delignification process could fulfil these requirements and stands today as a promising alternative. This work focus on understanding the fundamental chemistry behind the cleavage of B-O-4 ether bond present in 2-phenoxy-1-phenylethanol (PPE), a lignin model compound, with three acidic DES, including Propionic acid/Urea (PA:U), Lactic acid/Choline Chloride (LA:ChCl) and p-Toluenesulphonic acid/Choline chloride (pTSA:ChCl). The acidic nature of each DES influenced the efficiency of PPE cleavage and determined the extent of further side reactions of cleavage products. Although PA:U (2:1) demonstrated ability to dissolve lignin, it is unable to cleave B-O-4 ether linkage in PPE. On the other hand, LA:ChCl (10:1) allowed PPE cleavage, but an esterification between the PPE and lactic acid as well as oligomerization of lactic acid were detected. Among examined solvents, pTSA:ChCl (1:1) demonstrated the highest performance on the PPE cleavage, although the high acidity of this system lead to condensation of cleavage products at prolonged time. The presence of water decreases the ability of DES for the cleavage, but the extension of undesired side reactions was also reduced. Finally, the analysis of intermediates and products of the reactions allowed the identification of a chlorinated species of PPE that precedes the cleavage reaction. A kinetic study using pTSA:ChCl (1:1) and pTSA:ChBr (1:1) was performed to unveil the role of the halide counterion present in DES on the cleavage of <2=2 ether bond and a new reaction mechanism was herein proposed and supported by density functional theory (DFT) calculations.Altri ñ Celbi, Buckman, Crown Van Gelder, CTP, DS Smith Paper, ESKA, Essity, Holmen, ISPT, Mayr-Melnhof Eerbeek, Mets‰ Fibre, Mid Sweden University, Mondi, Omya, The Navigator Company, Sappi, Essity, Smurfit Kappa, Stora Enso, Eindhoven University of Technology, University of Aveiro, University of Twente, UPM, Valmet Technologies Oy, Voith Paper, VTT Technical Research Centre of Finland Ltd, WEPA and Zellstoff Pols.in publicatio