Tetra-arylborate lipophilic anions as targeting groups

Tetraphenylborate (TPB) anions traverse membranes but are excluded from mitochondria by the membrane potential (Δψ). TPB-conjugates also distributed across membranes in response to Δψ, but surprisingly, they rapidly entered cells. They accumulated within lysosomes following endocystosis. This pH-independent targeting of lysosomes makes possible new classes of probe and bioactive molecules

Neural stem cells traffic functional mitochondria via extracellular vesicles.

Neural stem cell (NSC) transplantation induces recovery in animal models of central nervous system (CNS) diseases. Although the replacement of lost endogenous cells was originally proposed as the primary healing mechanism of NSC grafts, it is now clear that transplanted NSCs operate via multiple mechanisms, including the horizontal exchange of therapeutic cargoes to host cells via extracellular vesicles (EVs). EVs are membrane particles trafficking nucleic acids, proteins, metabolites and metabolic enzymes, lipids, and entire organelles. However, the function and the contribution of these cargoes to the broad therapeutic effects of NSCs are yet to be fully understood. Mitochondrial dysfunction is an established feature of several inflammatory and degenerative CNS disorders, most of which are potentially treatable with exogenous stem cell therapeutics. Herein, we investigated the hypothesis that NSCs release and traffic functional mitochondria via EVs to restore mitochondrial function in target cells. Untargeted proteomics revealed a significant enrichment of mitochondrial proteins spontaneously released by NSCs in EVs. Morphological and functional analyses confirmed the presence of ultrastructurally intact mitochondria within EVs with conserved membrane potential and respiration. We found that the transfer of these mitochondria from EVs to mtDNA-deficient L929 Rho0 cells rescued mitochondrial function and increased Rho0 cell survival. Furthermore, the incorporation of mitochondria from EVs into inflammatory mononuclear phagocytes restored normal mitochondrial dynamics and cellular metabolism and reduced the expression of pro-inflammatory markers in target cells. When transplanted in an animal model of multiple sclerosis, exogenous NSCs actively transferred mitochondria to mononuclear phagocytes and induced a significant amelioration of clinical deficits. Our data provide the first evidence that NSCs deliver functional mitochondria to target cells via EVs, paving the way for the development of novel (a)cellular approaches aimed at restoring mitochondrial dysfunction not only in multiple sclerosis, but also in degenerative neurological diseases

Prazer e sofrimento de trabalhadoras de enfermagem que cuidam de idosos hospitalizados Placer y sufrimiento de las enfermeras que cuidan de ancianos hospitalizados Pleasure and suffering of nursing professionals in dealing with hospitalized elderly

Estudo exploratório-descritivo, com abordagem qualitativa, realizado com trabalhadores de enfermagem de um Hospital Universitário. Teve como objetivos conhecer o significado de ser idoso e identificar os fatores de prazer e sofrimento no cuidado aos idosos. Os dados foram coletados por meio de entrevista semiestruturada, submetidos à técnica da análise temática em torno de três eixos: o significado de ser idoso; os fatores de prazer e o sofrimento no cuidado ao idoso. As trabalhadoras de enfermagem associaram o idoso aos processos fisiológicos inerentes ao envelhecimento e ao surgimento de doenças. A superação de limites pelo idoso, a valorização dos cuidados prestados e a troca de experiências proporcionaram prazer às trabalhadoras. O sofrimento das trabalhadoras ocorreu diante de situações como abandono, descaso e iminência da morte dos idosos. Sugere-se organização de grupos de apoio e de espaços para as trabalhadoras compartilharem o prazer e o sofrimento no cuidado ao idoso.<br>Estudio exploratorio-descriptivo, con abordaje cualitativo, que fue realizado con enfermeras de un Hospital Universitario. Tuvo como objetivos conocer el significado de ser anciano e identificar los factores de placer y sufrimiento en el cuidado a los ancianos. Los datos fueron recolectados por medio de una entrevista semiestructurada, sometidos a la técnica del análisis temático basado en tres ejes: el significado de ser anciano; los factores de placer y sufrimiento en el cuidado del anciano. Las enfermeras relacionaron al anciano a los procesos fisiológicos inherentes al envejecimiento y al surgimiento de enfermedades. La superación de límites por el anciano, la valoración de los cuidados prestados y el intercambio de experiencias proporcionaron placer a las enfermeras. El sufrimiento de las enfermeras se presentó frente a situaciones como abandono, negligencia y inminente muerte de los ancianos. Se sugiere la organización de grupos de apoyo y de espacios para que las enfermeras puedan compartir el placer y el sufrimiento vivenciados en el cuidado al anciano.<br>This is an exploratory and descriptive study, with a qualitative approach conducted with nursing professionals of a University Hospital. It aimed to search for the meaning of being an elderly person and identify the pleasures and sufferings in taking care of elderly people. The data were collected through a semi-structured survey. The content of the surveys was analyzed by theme analysis. The data were analyzed based on three axes: the meaning of being an elderly patient; factors of pleasure; and factors of suffering in elderly health care. The overcoming of limits, valuing of health care rendered, and experience exchanges gave pleasure to the workers. The suffering of workers happened before situations like abandonment, lack of attention, and brewing death of the elderly people. The organization of supportive groups and spaces for workers to share the pleasure and suffering in elder caretaking

Continuous-flow CvFAP photodecarboxylation of palmitic acid under environmentally friendly conditions

The fatty acid photodecarboxylase from Chlorella variabilis NC64A (CvFAP) promotes the elimination of CO2 from fatty acids (Cn) producing the corresponding hydrocarbon (Cn-1). Therefore, this enzyme is of great biotechnological interest since it can be used in alternative biofuel production routes matching the concept of green chemistry. However, due to its recent discovery, this reaction still requires optimizations, which was the focus of the present work together with the application of continuous flow system. The results in batch reactors showed the importance of using high power LED lamps (300 W) to reduce the reaction time for full conversion (30 min, &gt;99%). In another approach, a continuous flow system demonstrated high potential, as it enabled full conversion with a half concentration of enzyme extract in a very short residence time of 15 min. Furthermore, the use of less expensive and sustainable light sources, not previously reported for reactions with CvFAP, were evaluated with full conversion (&gt;99%) after 1 h for continuous flow reactions using 300 W common white LED lamp and based preliminary batch reactions investigations using direct sunlight. Thus, important advances and new perspectives for CvFAP photodecarboxylation reactions could be achieved with the present report.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.BT/Biocatalysi

APOPT1/COA8 assists COX assembly and is oppositely regulated by UPS and ROS.

Loss-of-function mutations in APOPT1, a gene exclusively found in higher eukaryotes, cause a characteristic type of cavitating leukoencephalopathy associated with mitochondrial cytochrome c oxidase (COX) deficiency. Although the genetic association of APOPT1 pathogenic variants with isolated COX defects is now clear, the biochemical link between APOPT1 function and COX has remained elusive. We investigated the molecular role of APOPT1 using different approaches. First, we generated an Apopt1 knockout mouse model which shows impaired motor skills, e.g., decreased motor coordination and endurance, associated with reduced COX activity and levels in multiple tissues. In addition, by achieving stable expression of wild-type APOPT1 in control and patient-derived cultured cells we ruled out a role of this protein in apoptosis and established instead that this protein is necessary for proper COX assembly and function. On the other hand, APOPT1 steady-state levels were shown to be controlled by the ubiquitination-proteasome system (UPS). Conversely, in conditions of increased oxidative stress, APOPT1 is stabilized, increasing its mature intramitochondrial form and thereby protecting COX from oxidatively induced degradation