Pushing the limits of concertedness. A waltz of wandering carbocations.

Among the array of complex terpene-forming carbocation cyclization/rearrangement reactions, the so-called "triple shift" reactions are among the most unexpected. Such reactions involve the asynchronous combination of three 1,n-shifts into a concerted process, e.g., a 1,2-alkyl shift followed by a 1,3-hydride shift followed by a second 1,2-alkyl shift. This type of reaction so far has been proposed to occur during the biosynthesis of diterpenes and the sidechains of sterols. Here we describe efforts to push the limits of concertedness in this type of carbocation reaction by designing, and characterizing with quantum chemical computations, systems that could couple additional 1,n-shift events to a triple shift leading, in principle to quadruple, pentuple, etc. shifts. While our designs did not lead to clear-cut examples of quadruple, etc. shifts, they did lead to reactions with surprisingly flat energy surfaces where more than five chemical events connect reactants and plausible products. Ab initio molecular dynamics simulations demonstrate that the formal minima on these surfaces interchange on short timescales, both with each other and with additional unexpected structures, allowing us a glimpse into a very complex manifold that allows ready access to great structural diversity

Is Poly(Methyl Methacrylate) (PMMA) a suitable substrate for ALD?: A review

Poly (methyl methacrylate) (PMMA) is a thermoplastic synthetic polymer, which displays superior characteristics such as transparency, good tensile strength, and processability. Its performance can be improved by surface engineering via the use of functionalized thin film coatings, resulting in its versatility across a host of applications including, energy harvesting, dielectric layers and water purification. Modification of the PMMA surface can be achieved by atomic layer deposition (ALD), a vapor-phase, chemical deposition technique, which permits atomic-level control. However, PMMA presents a challenge for ALD due to its lack of active surface sites, necessary for gas precursor reaction, nucleation, and subsequent growth. The purpose of this review is to discuss the research related to the employment of PMMA as either a substrate, support, or masking layer over a range of ALD thin film growth techniques, namely, thermal, plasma-enhanced, and area-selective atomic layer deposition. It also highlights applications in the selected fields of flexible electronics, biomaterials, sensing, and photocatalysis, and underscores relevant characterization techniques. Further, it concludes with a prospective view of the role of ALD in PMMA processing.e Fundação para a Ciência e Tecnologia (FCT, Portugal)/PIDDAC through the Strategic Funds project reference UIDB/04650/2020-2023. This work was developed within the scope of the project CICECO-Aveiro Institute of Materials, UIDB/50011/2020 and UIDP/50011/2020, financed by national funds through the Portuguese Foundation for Science and Technology/MCTE

The influence of planning and response inhibition on cognitive functioning of Non-Psychotic unipolar depressed suicide attempters

Depression is one of the main risk factors for suicide. However, little is known about the intricate relationships among depressive symptomatology in unipolar depression, suicide risk, and the characteristics of executive dysfunction in depressed patients. We compared 20 non-psychotic unipolar depressed suicide attempters to 20 matching depressed non-attempters and to 20 healthy controls to further investigate the possible differences in neuropsychological performance. Depressed subjects were controlled for current suicidal ideation, and their neuropsychological profile was assessed using a range of measures of executive functioning, attention, verbal memory, processing speed, and psychomotor speed. Depressed groups were outperformed by healthy controls. Depressed attempters presented more cognitive impairment than depressed non-attempters on a simple Go/No-go response inhibition task and performed better than non-attempters on the Tower of London planning task. Depressed attempters were clearly distinguished by a deficit in response inhibition (Go/No-go commission errors). The normative planning performance (Tower of London extra moves) of the suicide attempters was unexpected, and this unanticipated finding calls for further research. Normative planning may indicate an increased risk of suicidal behavior.info:eu-repo/semantics/publishedVersio

Intrathecal injection of the secretome from ALS motor neurons regulated for miR-124 expression prevents disease outcomes in SOD1-G93A mice

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with short life expectancy and no effective therapy. We previously identified upregulated miR-124 in NSC-34-motor neurons (MNs) expressing human SOD1-G93A (mSOD1) and established its implication in mSOD1 MN degeneration and glial cell activation. When anti-miR-124-treated mSOD1 MN (preconditioned) secretome was incubated in spinal cord organotypic cultures from symptomatic mSOD1 mice, the dysregulated homeostatic balance was circumvented. To decipher the therapeutic potential of such preconditioned secretome, we intrathecally injected it in mSOD1 mice at the early stage of the disease (12-week-old). Preconditioned secretome prevented motor impairment and was effective in counteracting muscle atrophy, glial reactivity/dysfunction, and the neurodegeneration of the symptomatic mSOD1 mice. Deficits in corticospinal function and gait abnormalities were precluded, and the loss of gastrocnemius muscle fiber area was avoided. At the molecular level, the preconditioned secretome enhanced NeuN mRNA/protein expression levels and the PSD-95/TREM2/IL-10/arginase 1/MBP/PLP genes, thus avoiding the neuronal/glial cell dysregulation that characterizes ALS mice. It also prevented upregulated GFAP/Cx43/S100B/vimentin and inflammatory-associated miRNAs, specifically miR-146a/miR-155/miR-21, which are displayed by symptomatic animals. Collectively, our study highlights the intrathecal administration of the secretome from anti-miR-124-treated mSOD1 MNs as a therapeutic strategy for halting/delaying disease progression in an ALS mouse model.This research was funded by Santa Casa da Misericórdia de Lisboa: ELA-2015-002 (to DB); Fundação para a Ciência e a Tecnologia (FCT): PTDC/MED-NEU/31395/2017 (to D.B.), UIDB/UIDP/04138/2020, and UID/DTP/04138/2019-2020 (to iMed.ULisboa); Programa Operacional Regional de Lisboa and the Programa Operacional Competitividade e Internacionalização LISBOA-01-0145-FEDER-031395 (to D.B.); La Caixa Foundation and Francisco Luzón Foundation through project HR21-00931 (to D.B.); and an individual fellowship from FCT: SFRH/BD/129586/2017 (to M.B.). This work was also funded by the ICVS Scientific Microscopy Platform, a member of the national infrastructure of PPBI—Portuguese Platform of Bioimaging (PPBI-POCI-01-0145-FEDER-022122)

Revisiting ionic liquid structure‐property relationship: A critical analysis

grant number 201863/2014-6 UIDB/04378/2020 UIDB/50025/2020-2023 POCI-01-0145-FEDER-007688 PTDC/QUI-QFI/31508/2017 FCT-(ROTEIRO/0031/2013-PINFRA/22161/2016 UIDB/04378/2020In the last few years, ionic liquids (ILs) have been the focus of extensive studies concerning the relationship between structure and properties and how this impacts their application. Despite a large number of studies, several topics remain controversial or not fully answered, such as: the existence of ion pairs, the concept of free volume and the effect of water and its implications in the modulation of ILs physicochemical properties. In this paper, we present a critical review of state‐of-the‐art literature regarding structure–property relationship of ILs, we re‐examine analytical theories on the structure–property correlations and present new perspectives based on the existing data. The interrelation between transport properties (viscosity, diffusion, conductivity) of IL structure and free volume are analysed and discussed at a molecular level. In addition, we demonstrate how the analysis of microscopic features (particularly using NMR‐derived data) can be used to explain and predict macroscopic properties, reaching new perspectives on the properties and application of ILs.publishersversionpublishe

Oral hygiene and health education: implications for public health

Dental caries, a progressive infection caused by microorganisms, remain one of the most common diseases throughout the world. The mouth is an ideal environment for bacteria, and one of the best-known for being responsible for dental caries is the Streptococcus mutans.info:eu-repo/semantics/publishedVersio

Genomic and phenotypic characterization of Campylobacter fetus subsp. venerealis strains

Research Areas: MicrobiologyThe pathogenesis mechanisms of Campylobacter fetus subsp. venerealis (Cfv), the etiologic agent of Bovine Genital Campylobacteriosis remain elusive. This study evaluated the virulence potential and biovar characteristics of Cfv isolates (n = 13) by PCR screening of putative virulencefactor (VF) genes, Multilocus Sequence Typing (MLST) analysis, antimicrobial susceptibility to tetracycline, penicillin, enrofloxacin and streptomycin testing and whole-genome sequencing (WGS; n = 5), also comparing the latter with 26 other whole-genome sequences of Cfv strains. The putative VF genes encoding type IV secretion system of Cfv (virB2-virB11/virD4) were absent in 92% of isolates, including isolates from aborted foetuses, evidencing that these VF genes are not essential for Cfv pathogenicity. The parA gene, used as a Cfv diagnostic molecular target, was detected in only 3 of 13 isolates, invalidating its use for diagnosis purposes. Three novel sequence types were identified by MLST. Although no in vitro antimicrobial resistance was detected, WGS identified antimicrobial resistance-related genes, including those encoding the multidrug efflux pumps CmeABC and YkkCD, indicating that their presence is not enough to provide antimicrobial resistance. The SNP and accessory protein families analysis segregated the Cfv and Cfv biovar intermedius (Cfvi) strains into different clusters. In conclusion, this study evidenced virulence potential and biovar characteristics of Cfv and Cfvi, which are of relevance for the control of Bovine Genital Campylobacteriosis.info:eu-repo/semantics/publishedVersio

Treatment priorities in oncology: do we want to live longer or better?

OBJECTIVES: Despite the progress achieved in the fight against cancer over the past several years, assessing the needs, goals and preferences of patients with cancer is of the utmost importance for the delivery of health care. We sought to assess priorities regarding quantity versus quality of life among Brazilian patients, comparing them with individuals without cancer. METHODS: Using a questionnaire presenting four hypothetical cancer cases, we interviewed cancer patients, oncology health-care professionals and laypersons, most of whom had administrative functions in our hospital. RESULTS: A total of 214 individuals participated: 101 patients, 44 health-care professionals and 69 laypersons. The mean ages in the three groups were 56, 34 and 31 years old, respectively (