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In this study, the interplay among the phospholipid 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) as a model membrane, the nonsteroidal anti-inflammatory drug naproxen, and the saponin β-aescin are investigated. The naproxen amount was fixed to 10 mol%, and the saponin amount varies from 0.0 to 1.0 mol%. Both substances are common ingredients in pharmaceutics; therefore, it is important to obtain deeper knowledge of their impact on lipid membranes. The size and properties of the DMPC model membrane upon naproxen and aescin addition were characterized with differential scanning calorimetry (DSC), small- and wide-angle X-ray scattering (SAXS, WAXS), and photon correlation spectroscopy (PCS) in a temperature-dependent study. The interaction of all substances was dependent on the lipid phase state, which itself depends on the lipid’s main phase transition temperature Tm. The incorporation of naproxen and aescin distorted the lipid membrane structure and lowers Tm. Below Tm, the DMPC–naproxen–aescin mixtures showed a vesicle structure, and the insertion of naproxen and aescin influenced neither the lipid chain–chain correlation distance nor the membrane thickness. Above Tm, the insertion of both molecules instead induced the formation of correlated bilayers and a decrease in the chain–chain correlation distance. The presented data clearly confirm the interaction of naproxen and aescin with DMPC model membranes. Moreover, the incorporation of both additives into the model membranes is evidenced.

Aims: High levels of glucose and reactive carbonyl intermediates of its degradation pathway such as methylglyoxal (MG) may contribute to diabetic complications partly via increased generation of reactive oxygen species (ROS). This study focused on glutathione peroxidase-1 (GPx1) expression and the impact of carbonylation as an oxidative protein modification on GPx1 abundance and activity in human umbilical vein endothelial cells (HUVEC) under conditions of mild to moderate oxidative stress. Results: High extracellular glucose and MG enhanced intracellular ROS formation in HUVECs. Protein carbonylation was only transiently augmented pointing to an effective antioxidant defense in these cells. Nitric oxide synthase expression was decreased under hyperglycemic conditions but increased upon exposure to MG, whereas superoxide dismutase expression was not significantly affected. Increased glutathione peroxidase (GPx) activity seemed to compensate for a decrease in GPx1 protein due to enhanced degradation via the proteasome. Mass spectrometry analysis identified Lys-114 as a possible carbonylation target which provides a vestibule for the substrate H2O2 and thus enhances the enzymatic reaction. Innovation: Oxidative protein carbonylation has so far been associated with functional inactivation of modified target proteins mainly contributing to aging and age-related diseases. Here, we demonstrate that mild oxidative stress and subsequent carbonylation seem to activate protective cellular redox signaling pathways whereas severe oxidative stress overwhelms the cellular antioxidant defense leading to cell damage. Conclusions: This study may contribute to a better understanding of redox homeostasis and its role in the development of diabetes and related vascular complications. Keywords: Protein carbonylation, Reactive oxygen species, Hyperglycemia, Glutathione peroxidase-1, Endothelial cells

Hsp70 participates in a broad spectrum of protein folding processes extending from nascent chain folding to protein disaggregation. This versatility in function is achieved through a diverse family of J-protein cochaperones that select substrates for Hsp70. Substrate selection is further tuned by transient complexation between different classes of J-proteins, which expands the range of protein aggregates targeted by metazoan Hsp70 for disaggregation. We assessed the prevalence and evolutionary conservation of J-protein complexation and cooperation in disaggregation. We find the emergence of a eukaryote-specific signature for interclass complexation of canonical J-proteins. Consistently, complexes exist in yeast and human cells, but not in bacteria, and correlate with cooperative action in disaggregation in vitro. Signature alterations exclude some J-proteins from networking, which ensures correct J-protein pairing, functional network integrity and J-protein specialization. This fundamental change in J-protein biology during the prokaryote-to-eukaryote transition allows for increased fine-tuning and broadening of Hsp70 function in eukaryotes.

MASSCHELEIN, Jan; SIMONS, Maarten. Em defesa da escola: uma questão pública. 2 ed. Belo Horizonte: Autêntica, 2014. Coleção: Experiência e Sentido.

O presente texto aborda alguns desdobramentos e reflexões acerca de práticas desenvolvidas na oficina Geografia Experimental do Corpo, – cujo intuito é propiciar ao participante um percurso sensório – espacial sem o uso da visão. Com isso visa-se produzir e discutir “mapas sensacionais” a partir desse percurso. Tal oficina teve início em de práticas relacionadas à iniciação cartografia com turmas do 5º ano do fundamental de uma escola estadual localizada no município de Florianópolis – SC, alcançando outras dimensões fora da escola. Com base no material produzido nessa oficina discorre-se sobre as suas possibilidades e limitações, bem como brevemente, seus processos de formação e evolução. Partindo desse contexto de formação e prática em educação, busca-se pensar sobre dois pontos que se sobressaem no processo da oficina: a questão da relação do visível (olhar) e do corpo com espaço; e as cartografias oriundas dessa relação, em um contexto de experiência em educação na área de Geografia. Em paralelo a essas reflexões, analisa-se essa proposta de oficina considerando-a como uma ferramenta prática que tenta fazer com que algo nos passe, buscando uma aproximação ao conceito de experiência em Jorge Larrosa, e que se relaciona com um modo de fazer e pensar cartografia.

Protein aggregates are the hallmark of stressed and ageing cells, and characterize several pathophysiological states (1, 2). Healthy metazoan cells effectively eliminate intracellular protein aggregates (3, 4), indicating that efficient disaggregation and/or degradation mechanisms exist. However, metazoans lack the key heat-shock protein disaggregase HSP100 of non-metazoan HSP70-dependent protein disaggregation systems (5, 6), and the human HSP70 system alone, even with the crucial HSP110 nucleotide exchange factor, has poor disaggregation activity in vitro (4, 7). This unresolved conundrum is central to protein quality control biology. Here we show that synergic cooperation between complexed J-protein co-chaperones of classes A and B unleashes highly efficient protein disaggregation activity in human and nematode HSP70 systems. Metazoan mixed-class J-protein complexes are transient, involve complementary charged regions conserved in the J-domains and carboxy-terminal domains of each J-protein class, and are flexible with respect to subunit composition. Complex formation allows J-proteins to initiate transient higher order chaperone structures involving HSP70 and interacting nucleotide exchange factors. A network of cooperative class A and B J-protein interactions therefore provides the metazoan HSP70 machinery with powerful, flexible, and finely regulatable disaggregase activity and a further level of regulation crucial for cellular protein quality control., To investigate the possibility of a potent protein disaggregation activity in metazoans, we focused on the HSP70 chaperone system, which displays some in vitro capacity to disentangle and refold aggregated [...]

The extreme demand volatility caused by corona virus 2019 (COVID‐19) overwhelmed most preemptive measures enacted by firms to mitigate disruptions in their supply chains. This led to the rapid implementation of reactive measures to provide business continuity. The operations and supply chain management literature has grouped these reactive techniques into those that involve the reconfiguration of firm resources and those that involve changes to its decision‐making processes. Unfortunately, little of this work has empirically assessed the efficacy of individual reactive techniques on business continuity after the onset of a disruption such as COVID‐19. The research reported in this paper addresses this gap through an experimental design and discrete‐event simulation to empirically test the impact on firm outcomes of resource reconfiguration techniques versus those related to adaptive decision‐making processes. Data from a canned foods manufacturer is used to populate the simulation and isolate the impact of these reactive changes implemented in March 2020 at the beginning of the COVID‐19 disruption on the attainment of business continuity in the 3 months following the COVID‐19 disruption. The results show that for this company, decision‐making changes—specifically changes to planning process cadence and time horizon—had more impact on business continuity than those focused on resource reconfiguration (increasing capacity through stock keeping unit (SKU) prioritization and increasing the number of shifts). These results, in addition to qualitative data collected from company executives to provide context for the modeling results, are used to provide insights that are generalizable to many firms. [ABSTRACT FROM AUTHOR]