Signaling Circuits on the Golgi Complex Cancino, Jorge; Luini, Alberto
Traffic (Copenhagen, Denmark),
February 2013, Letnik:
14, Številka:
2
Journal Article
Recenzirano
Numerous components of signaling pathways involved in key cellular processes reside on the Golgi complex. Here, we will focus on the roles of signaling proteins that regulate cargo trafficking along ...the anterograde and retrograde pathways. Emphasis will also be put on the effects of these regulatory proteins on the maintenance of the structure and function of the Golgi, and in particular on the phosphorylation of key components of the transport machinery. These pathways position the Golgi complex as a central hub in the regulation of cell signaling. To date, however, the activation and coordination of these signaling molecules remain a mystery. Being able to describe the interplay between several of these signaling pathways and secretion, and the flow of information through these pathways, will help us to understand how the secretory machinery works and how it interacts with other cellular functions. This will also advance our understanding of how the secretory pathway functions under physiological circumstances, and how its dysregulation can initiate pathological conditions.
Neutrophils play a crucial role in eliminating bacteria that invade the human body; however, cathepsin G can induce biofilm formation in a non-biofilm-forming Staphylococcus epidermidis 1457 strain, ...suggesting that neutrophil proteases may be involved in biofilm formation. Cathepsin G, cathepsin B, proteinase-3, and metalloproteinase-9 (MMP-9) from neutrophils were tested on the biofilm induction in commensal (skin isolated) and clinical non-biofilm-forming S. epidermidis isolates. From 81 isolates, 53 (74%) were aap+, icaA−, icaD− genotype, and without the capacity of biofilm formation under conditions of 1% glucose, 4% ethanol or 4% NaCl, but these 53 non-biofilm-forming isolates induced biofilm by the use of different neutrophil proteases. Of these, 62.3% induced biofilm with proteinase-3, 15% with cathepsin G, 10% with cathepsin B and 5% with MMP -9, where most of the protease-induced biofilm isolates were commensal strains (skin). In the biofilm formation kinetics analysis, the addition of phenylmethylsulfonyl fluoride (PMSF; a proteinase-3 inhibitor) showed that proteinase-3 participates in the cell aggregation stage of biofilm formation. A biofilm induced with proteinase-3 and DNAse-treated significantly reduced biofilm formation at an early time (initial adhesion stage of biofilm formation) compared to untreated proteinase-3-induced biofilm (p < 0.05). A catheter inoculated with a commensal (skin) non-biofilm-forming S. epidermidis isolate treated with proteinase-3 and another one without the enzyme were inserted into the back of a mouse. After 7 days of incubation period, the catheters were recovered and the number of grown bacteria was quantified, finding a higher amount of adhered proteinase-3-treated bacteria in the catheter than non-proteinase-3-treated bacteria (p < 0.05). Commensal non-biofilm-forming S. epidermidis in the presence of neutrophil cells significantly induced the biofilm formation when multiplicity of infection (MOI) 1:0.01 (neutrophil:bacteria) was used, but the addition of a cocktail of protease inhibitors impeded biofilm formation. A neutrophil:bacteria assay did not induce neutrophil extracellular traps (NETs). Our results suggest that neutrophils, in the presence of commensal non-biofilm-forming S. epidermidis, do not generate NETs formation. The effect of neutrophils is the production of proteases, and proteinase-3 releases bacterial DNA at the initial adhesion, favoring cell aggregation and subsequently leading to biofilm formation.
Maintaining the optimal performance of cell processes and organelles is the task of auto-regulatory systems. Here we describe an auto-regulatory device that helps to maintain homeostasis of the ...endoplasmic reticulum (ER) by adjusting the secretory flux to the cargo load. The cargo-recruiting subunit of the coatomer protein II (COPII) coat, Sec24, doubles as a sensor of folded cargo and, upon cargo binding, acts as a guanine nucleotide exchange factor to activate the signaling protein Gα12 at the ER exit sites (ERESs). This step, in turn, activates a complex signaling network that activates and coordinates the ER export machinery and attenuates proteins synthesis, thus preventing large fluctuations of folded and potentially active cargo that could be harmful to the cell or the organism. We call this mechanism AREX (autoregulation of ER export) and expect that its identification will aid our understanding of human physiology and diseases that develop from secretory dysfunction.
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•ER exit sites are endowed with an auto-regulatory signaling complex called AREX•The COPII subunit Sec24 senses folded cargo and activates the AREX signaling network•AREX responds to folded cargo fluxes by regulating cargo export and protein synthesis•AREX maintains potentially harmful folded cargo in the ER at steady low levels
By sensing the load of folded ER lumenal proteins, the COPII subunit Sec24 directs a signaling cascade that allows secretory pathway flux to respond to the abundance of cargo.
Objetivo: describir los aspectos éticos a considerar en el asentimiento de los adolescentes para participar en investigaciones.Material y Método: Revisión narrativa de la literatura en las bases de ...datos científicas PUBMED y BVS, entre los años 2010-2021, la búsqueda fue realizada en inglés, utilizando descriptores MeSH y DeCS. De 77 artículos iniciales, fueron seleccionados un total de 12 artículos para su análisis.Resultados: Comúnmente se utilizó la edad, en lugar de evaluar directamente la capacidad para comprender los problemas y tomar una decisión informada sobre participar en la investigación. Esta capacidad se encuentra influenciada por la edad, el contexto y el desarrollo. La toma de decisiones de los adolescentes fue sustancialmente diferente en presencia de pares. Es necesario un equilibrio entre el reconocimiento de la autonomía emergente en adolescentes, sus ritmos diferenciales de desarrollo y su respuesta aún no completamente madura al riesgo personal.Conclusiones: Es necesario generar respuestas y estrategias que resguarden tanto la seguridad como el respeto hacia los adolescentes, centradas las características propias tanto del grupo etario como individuales, logrando unificar mecanismos válidos en la de determinación de la capacidad de asentir, integrando criterios desde las ciencias respecto a cognición, maduración y desarrollo, psicología y ética.
Biological control has been the most commonly researched control tactic within fruit fly management programs. For the first time, a review is carried out covering parasitoids and predators of fruit ...flies (Tephritidae) from the Americas and Hawaii, presenting the main biological control programs in this region. In this work, 31 species of fruit flies of economic importance are considered in the genera Anastrepha (11), Rhagoletis (14), Bactrocera (4), Ceratitis (1), and Zeugodacus (1). In this study, a total of 79 parasitoid species of fruit flies of economic importance are listed and, from these, 50 are native and 29 are introduced. A total of 56 species of fruit fly predators occur in the Americas and Hawaii.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Extracellular vesicles (EVs) have shown great potential for targeted therapy, as they have a natural ability to pass through biological barriers and, depending on their origin, can preferentially ...accumulate at defined sites, including tumors. Analyzing the potential of EVs to target specific cells remains challenging, considering the unspecific binding of lipophilic tracers to other proteins, the limitations of fluorescence for deep tissue imaging and the effect of external labeling strategies on their natural tropism. In this work, we determined the cell-type specific tropism of B16F10-EVs towards cancer cell and metastatic tumors by using fluorescence analysis and quantitative gold labeling measurements. Surface functionalization of plasmonic gold nanoparticles was used to promote indirect labeling of EVs without affecting size distribution, polydispersity, surface charge, protein markers, cell uptake or in vivo biodistribution. Double-labeled EVs with gold and fluorescent dyes were injected into animals developing metastatic lung nodules and analyzed by fluorescence/computer tomography imaging, quantitative neutron activation analysis and gold-enhanced optical microscopy.
We determined that B16F10 cells preferentially take up their own EVs, when compared with colon adenocarcinoma, macrophage and kidney cell-derived EVs. In addition, we were able to detect the preferential accumulation of B16F10 EVs in small metastatic tumors located in lungs when compared with the rest of the organs, as well as their precise distribution between tumor vessels, alveolus and tumor nodules by histological analysis. Finally, we observed that tumor EVs can be used as effective vectors to increase gold nanoparticle delivery towards metastatic nodules.
Our findings provide a valuable tool to study the distribution and interaction of EVs in mice and a novel strategy to improve the targeting of gold nanoparticles to cancer cells and metastatic nodules by using the natural properties of malignant EVs.
This study investigated the effect of 4 weeks of high-intensity interval training (HIIT) with specific techniques (TS-G) vs. repeated sprints (RS-G) and analyzed the inter-individual variability ...classified into responders (Rs) and non-responders (NRs) on sport-related fitness in taekwondo (TKD) athletes. Athletes of both genders (
n
= 12) were randomly assigned into TS-G and RS-G groups. Both groups trained 3 days/week for 4 weeks two blocks of three rounds of 2 min of activity (4-s of all-out efforts with 28-s dynamical pauses) with 1 min of recovery in between and 5 min between blocks during their regular training. The related sport fitness assessments included squat jump (SJ), countermovement jump (CMJ), multiple frequency speed of kick test (FSKT
MULT
), specifically total kicks and Kick Decrement Index (KDI), and 20-m shuttle run (20MSR). Relevant results indicate a significant effect of the time factor in both groups for SJ performance and a significant decrease for KDI in RS-G. In addition, an improvement in performance according to the effect size analysis in the TS-G in total kicks, KDI, and 20MSR. Complementarily, a higher proportion of athlete Rs was reported in TS-G vs. RS-G for SJ (50% vs. 30.3%, respectively), CMJ, and total kicks (16.6% vs. 0%). In conclusion, the addition to the regular training of a HIIT with specific-techniques and repeated-sprints associated with intervals and similar structure of the combat during 4 weeks of training can improve the concentric characteristics of lower limb performance, although they were not the sufficient stimuli in the other components of TKD-related fitness.
The authors compared the effects of bodyweight resistance training at moderate- or high-speed conditions on muscle power, velocity of movement, and functional performance in older females. In a ...randomized, single-blinded noncontrolled trial, participants completed 12 weeks (three sessions/week) of bodyweight resistance training at high (n = 14; age = 70.6 ± 4.3 years) or moderate (n = 12; age = 72.8 ± 4.2 years) speeds. Data were analyzed with an analysis of variance (Group × Time) with α level set at <.05. After the intervention, timed up and go test performance (p < .05) and the rising from a chair test mean (22.4%) and maximal velocity (28.5%), mean (24.4%) and maximal power (27.7%), normalized mean (25.1%), and normalized maximal power (28.5%) increased in the high-speed group (p < .05). However, the moderate-speed group achieved no improvements (Δ6.7-14.4%; p > .2). The authors conclude that high-speed bodyweight resistance training is an effective and economically practical strategy to improve the functional capacity of older women relevant to daily life activities.
Purpose The purpose of this study was to determine the behavior of creatine kinase before and after the execution of a pre-activation protocol with intra-set variable resistance in order to generate ...post-activation potentiation in female athletes. Participants and Methods Six sprint women were part of the study. The study had a quasi-experimental intra-participant design. The experimental condition included a pre-activation with intra-set variable resistance + 1 minute rest + 30-m sprint × 3. The variables were metabolic creatine kinase, total creatine kinase, and 30-m sprints. Results Both the experimental condition and the control condition showed an increase in creatine kinase and total creatine kinase 24 hours post-effort. Only the experimental condition showed improvement in 30-m sprints after the pre-activation with intra-set variable resistance. Conclusion All those sessions oriented to increasing strength levels with a pre-activation protocol through intra-set variable resistance must consider rests longer than 24 hours between sessions in order not to increase creatine kinase in female athletes significantly.
Inter-organelle signalling has essential roles in cell physiology encompassing cell metabolism, aging and temporal adaptation to external and internal perturbations. How such signalling coordinates ...different organelle functions within adaptive responses remains unknown. Membrane traffic is a fundamental process in which membrane fluxes need to be sensed for the adjustment of cellular requirements and homeostasis. Studying endoplasmic reticulum-to-Golgi trafficking, we found that Golgi-based, KDEL receptor-dependent signalling promotes lysosome repositioning to the perinuclear area, involving a complex process intertwined to autophagy, lipid-droplet turnover and Golgi-mediated secretion that engages the microtubule motor protein dynein-LRB1 and the autophagy cargo receptor p62/SQSTM1. This process, here named 'traffic-induced degradation response for secretion' (TIDeRS) discloses a cellular mechanism by which nutrient and membrane sensing machineries cooperate to sustain Golgi-dependent protein secretion.
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