Regeneration of the peripheral nerve - Development and evaluation of guide tubes of biodegradable polymer

Damage to peripheral nerve fibers results in axonal loss and demyelination followed by regeneration and remyelination under optimal conditions with the possibility of some functional recovery. The experimental challenge is to accelerate axonal regeneration to promote reinnervation and improve functional recovery after peripheral nerve injury. In the past few decades, different types of biological or artificial guide tubes have been developed to bridge the gap of a sectioned nerve, to limit the fibrosis process and to orient the regenerating fibers towards the distal stump. Chitosan is widely used for biomedical applications, including crosslinked with other materials. In this work, chitosan guide tubes were produced and implanted using the rat sciatic nerve animal model. Functional tests were performed as well as a mechanical and structural characterization of the guide tubes. (c) 2017 IEEE

Occurrence and Phylogenetic Analysis of Zoonotic Enteropathogenic Protist Parasites in Asymptomatic Domestic Ruminants from Portugal

Enteropathogenic parasites are of significant concern for public health due to their zoonotic potential and their impact on human and animal health. In this study, we investigated their occurrence and characterized these enteropathogens in asymptomatic domestic ruminants from Portugal. A total of 302 stool samples were collected from cattle (n = 166), sheep (n = 73), and goats (n = 63) in various regions of Portugal and tested for Cryptosporidium spp., Giardia duodenalis, Enterocytozoon bieneusi, Blastocystis sp., and Balantioides coli by PCR. The occurrence of Cryptosporidium spp. was found to be 12.7% (8/63, 95% confidence interval [CI]: 5.65–23.5) in goats; however, no sample was found to be positive for Cryptosporidium spp. in cattle and sheep. For E. bieneusi, 6.35% (4/63; 95%CI: 1.76–15.47) of goats were found to be positive; however, no cattle or sheep were found to be positive. Blastocystis sp. was found in sheep (9.59%; 7/73; 95% [CI]: 0.394–18.76) and goats (12.70%; 8/63; 95% [CI]: 5.65–23.50) but none was found in cattle. No positive results for G. duodenalis or B. coli were detected in this study. This study provides essential baseline information for understanding the silent shedding and epidemiology of these enteropathogens in Portugal, contributing to overall livestock health and related occupational safety. Raising awareness among consumers, veterinarians, and farm owners is crucial to minimize the risk of transmission and promote effective disease control strategies.This research was funded by the Fundação para Ciência e Tecnologia (FCT), grant number 2021.09461.BD.Sérgio Santos-Silva thanks the Fundação para a Ciência e a Tecnologia (FCT) for the financial support of his PhD work under the 2021 scholarship, 09461.BD contract through the Maria de Sousa-2021 program. This work was financed by national funds through the FCT—Fundação para a Ciência e a Tecnologia, I.P., under the projects UIDB/04750/2020 and LA/P/0064/2020

Hepatitis B virus genotypes and resistance mutations in patients under long term lamivudine therapy: characterization of genotype G in Brazil

Submitted by Sandra Infurna ([email protected]) on 2018-08-02T14:46:32Z No. of bitstreams: 1 kiciamro_etal_IOC_2008.pdf: 506267 bytes, checksum: f7829a89c2411e97f96c3d5a4123f436 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2018-08-02T14:57:58Z (GMT) No. of bitstreams: 1 kiciamro_etal_IOC_2008.pdf: 506267 bytes, checksum: f7829a89c2411e97f96c3d5a4123f436 (MD5)Made available in DSpace on 2018-08-02T14:57:58Z (GMT). No. of bitstreams: 1 kiciamro_etal_IOC_2008.pdf: 506267 bytes, checksum: f7829a89c2411e97f96c3d5a4123f436 (MD5) Previous issue date: 2008Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Virologia Molecular. Rio de Janeiro, RJ. Brasil.Universidade Federal de Mato Grosso. Faculdade de Ciências Médicas. Núcleo de Estudos de Doenças Infecciosas e Tropicais. Cuiabá, MT, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Virologia Molecular. Rio de Janeiro, RJ. Brasil / Fundação Municipal de Saúde de Petrópolis. Hospital Alcides Carneiro. Petrópolis, RJ. Brasil.Universidade Federal do Estado do Rio de Janeiro. Hospital Universitário Gaffrée e Guinle. Rio de Janeiro, RJ, Brasil.Universidade Federal do Estado do Rio de Janeiro. Hospital Universitário Gaffrée e Guinle. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Virologia Molecular. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Virologia Molecular. Rio de Janeiro, RJ. Brasil.Lamivudine is an oral nucleoside analogue widely used for the treatment of chronic hepatitis B. The main limitation of lamivudine use is the selection of resistant mutations that increases with time of utilization. Hepatitis B virus (HBV) isolates have been classified into eight genotypes (A to H) with distinct geographical distributions. HBV genotypes may also influence pathogenic properties and therapeutic features. Here, we analyzed the HBV genotype distribution and the nature and frequency of lamivudine resistant mutations among 36 patients submitted to lamivudine treatment for 12 to 84 months

On finite monoids of cellular automata.

For any group G and set A, a cellular automaton over G and A is a transformation τ:AG→AGτ:AG→AG defined via a finite neighbourhood S⊆GS⊆G (called a memory set of ττ) and a local function μ:AS→Aμ:AS→A. In this paper, we assume that G and A are both finite and study various algebraic properties of the finite monoid CA(G,A)CA(G,A) consisting of all cellular automata over G and A. Let ICA(G;A)ICA(G;A) be the group of invertible cellular automata over G and A. In the first part, using information on the conjugacy classes of subgroups of G, we give a detailed description of the structure of ICA(G;A)ICA(G;A) in terms of direct and wreath products. In the second part, we study generating sets of CA(G;A)CA(G;A). In particular, we prove that CA(G,A)CA(G,A) cannot be generated by cellular automata with small memory set, and, when G is finite abelian, we determine the minimal size of a set V⊆CA(G;A)V⊆CA(G;A) such that CA(G;A)=⟨ICA(G;A)∪V⟩CA(G;A)=⟨ICA(G;A)∪V⟩

The long noncoding RNA neuroLNC regulates presynaptic activity by interacting with the neurodegeneration-associated protein TDP-43

The cellular and the molecular mechanisms by which long noncoding RNAs (lncRNAs) may regulate presynaptic function and neuronal activity are largely unexplored. Here, we established an integrated screening strategy to discover lncRNAs implicated in neurotransmitter and synaptic vesicle release. With this approach, we identified neuroLNC, a neuron-specific nuclear lncRNA conserved from rodents to humans. NeuroLNC is tuned by synaptic activity and influences several other essential aspects of neuronal development including calcium influx, neuritogenesis, and neuronal migration in vivo. We defined the molecular interactors of neuroLNC in detail using chromatin isolation by RNA purification, RNA interactome analysis, and protein mass spectrometry. We found that the effects of neuroLNC on synaptic vesicle release require interaction with the RNA-binding protein TDP-43 (TAR DNA binding protein-43) and the selective stabilization of mRNAs encoding for presynaptic proteins. These results provide the first proof of an lncRNA that orchestrates neuronal excitability by influencing presynaptic function

Chiral Polymerization in Open Systems From Chiral-Selective Reaction Rates

We investigate the possibility that prebiotic homochirality can be achieved exclusively through chiral-selective reaction rate parameters without any other explicit mechanism for chiral bias. Specifically, we examine an open network of polymerization reactions, where the reaction rates can have chiral-selective values. The reactions are neither autocatalytic nor do they contain explicit enantiomeric cross-inhibition terms. We are thus investigating how rare a set of chiral-selective reaction rates needs to be in order to generate a reasonable amount of chiral bias. We quantify our results adopting a statistical approach: varying both the mean value and the rms dispersion of the relevant reaction rates, we show that moderate to high levels of chiral excess can be achieved with fairly small chiral bias, below 10%. Considering the various unknowns related to prebiotic chemical networks in early Earth and the dependence of reaction rates to environmental properties such as temperature and pressure variations, we argue that homochirality could have been achieved from moderate amounts of chiral selectivity in the reaction rates.Comment: 15 pages, 6 figures, accepted for publication in Origins of Life and Evolution of Biosphere

Reversible Keap1 inhibitors are preferential pharmacological tools to modulate cellular mitophagy

Mitophagy orchestrates the autophagic degradation of dysfunctional mitochondria preventing their pathological accumulation and contributing to cellular homeostasis. We previously identified a novel chemical tool (hereafter referred to as PMI), which drives mitochondria into autophagy without collapsing their membrane potential (ΔΨm). PMI is an inhibitor of the protein-protein interaction (PPI) between the transcription factor Nrf2 and its negative regulator, Keap1 and is able to up-regulate the expression of autophagy-associated proteins, including p62/SQSTM1. Here we show that PMI promotes mitochondrial respiration, leading to a superoxide-dependent activation of mitophagy. Structurally distinct Keap1-Nrf2 PPI inhibitors promote mitochondrial turnover, while covalent Keap1 modifiers, including sulforaphane (SFN) and dimethyl fumarate (DMF), are unable to induce a similar response. Additionally, we demonstrate that SFN reverses the effects of PMI in co-treated cells by reducing the accumulation of p62 in mitochondria and subsequently limiting their autophagic degradation. This study highlights the unique features of Keap1-Nrf2 PPI inhibitors as inducers of mitophagy and their potential as pharmacological agents for the treatment of pathological conditions characterized by impaired mitochondrial quality control

Astrocyte-derived TNF and glutamate critically modulate microglia activation by methamphetamine

Methamphetamine (Meth) is a powerful illicit psychostimulant, widely used for recreational purposes. Besides disrupting the monoaminergic system and promoting oxidative brain damage, Meth also causes neuroinflammation, contributing to synaptic dysfunction and behavioral deficits. Aberrant activation of microglia, the largest myeloid cell population in the brain, is a common feature in neurological disorders triggered by neuroinflammation. In this study, we investigated the mechanisms underlying the aberrant activation of microglia elicited by Meth in the adult mouse brain. We found that binge Meth exposure caused microgliosis and disrupted risk assessment behavior (a feature that usually occurs in individuals who abuse Meth), both of which required astrocyte-to-microglia crosstalk. Mechanistically, Meth triggered a detrimental increase of glutamate exocytosis from astrocytes (in a process dependent on TNF production and calcium mobilization), promoting microglial expansion and reactivity. Ablating TNF production, or suppressing astrocytic calcium mobilization, prevented Meth-elicited microglia reactivity and re-established risk assessment behavior as tested by elevated plus maze (EPM). Overall, our data indicate that glial crosstalk is critical to relay alterations caused by acute Meth exposure.This work was financed by FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT— Fundação para a Ciência e a Tecnologia/Ministério da Ciência (FCT), Tecnologia e Ensino Superior in the framework of the project POCI-01-0145-FEDER-030647 (PTDC/ SAU-TOX/30647/2017) in TS lab. FEDER Portugal (Norte-01-0145-FEDER000008000008—Porto Neurosciences and Neurologic Disease Research Initiative at I3S, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF); FCOMP-01-0124-FEDER-021333). CCP and RS hold employment contracts financed by national funds through FCT –in the context of the program-contract described in paragraphs 4, 5, and 6 of art. 23 of Law no. 57/ 2016, of August 29, as amended by Law no. 57/2017 of July 2019. TC, TOA, AFT, JB, AIS and AM were supported by FCT (SFRH/BD/117148/2016, SFRH/BD/147981/2019, 2020.07188.BD, PD/BD/135450/2017, SFRH/BD/144324/2019, and IF/00753/2014). Work in JBR lab was supported by the FCT project PTDC/ MED-NEU/31318/2017. JFO was also supported by FCT projects PTDC/MED-NEU/31417/2017 and POCI-01- 0145-FEDER-016818; Bial Foundation Grants 207/14 and 037/18, by National funds, through FCT - project UIDB/50026/2020; and by the projects NORTE-01-0145-FEDER000013 and NORTE-01-0145-FEDER-000023, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). Funding of i3S Scientific Platforms: Advanced Light Microscopy (ALM), a member of the national infrastructure PPBI-Portuguese Platform of BioImaging (POCI-01–0145-FEDER022122); and Genomics through GenomePT project (POCI-01-0145-FEDER-022184), supported by COMPETE 2020—Operational Programme for Competitiveness and Internationalization (POCI), Lisboa Portugal Regional Operational Programme (Lisboa2020), Algarve Portugal Regional Operational Programme (CRESC Algarve2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), and by FCT