scholarly journals CELL NON-AUTONOMOUS SEROTONIN SIGNALING MEDIATES STRESS RESISTANCE AND LONGEVITY

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S730-S730
Author(s):  
Scott Leiser ◽  
Hillary Miller ◽  
Shijiao Huang

Abstract The ability of organisms to perceive and respond to their environment is crucial to their long-term survival. Recent studies in model organisms identify signaling pathways that perceive environmental stress and cell non-autonomously modify systemic physiology. These pathways often originate in the neurons, where key cells monitor the external environment for changes including food availability, air-quality, and the presence of dangerous toxins. Our previous work identified a key role for serotonin signaling in the induction of flavin-containing monooxygenase-2 (fmo-2) downstream of hypoxic signaling. fmo-2 expression is necessary and sufficient to promote stress resistance and longevity downstream of multiple genetic pathways, making it a useful tool for identifying key components of these pathways. Our current data defines environments, pathways, and signaling molecules that induce fmo-2 and subsequently increase lifespan. Our resulting data define key roles for serotonin signaling and fmo-2 that rely upon the perception of oxygen and food.

2020 ◽  
Vol 13 ◽  
pp. 175628482092419
Author(s):  
Alexandra Gangi ◽  
Shelly C. Lu

Patients with colorectal cancer (CRC) have benefited significantly from advances in multimodal treatment with significant improvements in long-term survival. More patients are currently being treated with surgical resection or ablation following neoadjuvant or adjuvant chemotherapy. However, several cytotoxic agents that are administered routinely have been linked to liver toxicities that impair liver function and regeneration. Recognition of chemotherapy-related liver toxicity emphasizes the importance of multidisciplinary planning to optimize care. This review aims to summarize current data on multimodal treatment concepts for CRC, provide an overview of liver damage caused by commonly administered chemotherapeutic agents, and evaluate currently suggested protective agents.


2008 ◽  
Vol 22 (5) ◽  
pp. 297-304
Author(s):  
Jing Zhong ◽  
Sizong Wu ◽  
Jun Li

This study compares two high-tech firms in terms of their differences in organizational characteristics and learning activities beyond the boundaries. It finds that the larger company continuously develops new technology to achieve long-term survival through a balance between exploration and exploitation while the smaller enterprise grows quickly by leveraging focused technology and core business. The innovation-oriented firm gives more emphasis to learning beyond its knowledge boundary and the customer-oriented firm focuses on learning beyond its organizational boundary. The two firms' sustainable development illustrates two strategies to adapt to the complexity of the external environment.


2021 ◽  
Vol 8 (1) ◽  
pp. 4
Author(s):  
Anna B. Frerichs ◽  
Mingwei Huang ◽  
Sébastien C. Ortiz ◽  
Christina M. Hull

Spores are essential for the long-term survival of many diverse organisms, due to their roles in reproduction and stress resistance. In the environmental human fungal pathogen, Cryptococcus, basidiospores are robust cells with the ability to cause disease in animal models of infection. Here we describe methods for producing and purifying Cryptococcus basidiospores in quantities sufficient for large-scale analyses. The production of high numbers of pure spores has facilitated the development of new assays, including quantitative germination assays, and enabled transcriptomic, proteomic, and virulence studies, leading to discoveries of behaviors and properties unique to spores and spore-mediated disease.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9011-9011 ◽  
Author(s):  
Natasha B. Leighl ◽  
Matthew David Hellmann ◽  
Rina Hui ◽  
Enric Carcereny Costa ◽  
Enriqueta Felip ◽  
...  

9011 Background: Pembrolizumab (pembro) is approved as first-line (1L) treatment for advanced NSCLC patients (pts) with PD-L1 tumor proportion score (TPS) ≥50% and as treatment for previously treated advanced NSCLC pts with PD-L1 TPS ≥1%. Here we present 3-y OS results for pts enrolled in KEYNOTE-001 (NCT01295827), the first trial evaluating pembro in advanced NSCLC pts. Methods: 550 pts received pembro 2 or 10 mg/kg Q3W or 10 mg/kg Q2W until intolerable toxicity, progression, or investigator or pt decision to withdraw. PD-L1 expression was assessed by IHC using the 22C3 antibody. Survival was assessed every 2 mo after treatment discontinuation. Results: 550 advanced NSCLC pts enrolled; 101 were first line (1L), and 449 were previously treated. As of the Sept 1, 2016, data cutoff, median follow-up duration was 34.5 mo (range, 25.7-51.5 mo); 8 (7.9%) 1L pts and 28 (6.2%) previously treated pts were still on treatment. 3-y OS was 26.4% (95% CI, 14.3%-40.1%) in 1L pts and 19% (95% CI, 15.0%-23.4%) in previously treated pts. 3-y OS rate and median OS by PD-L1 status are in the Table. Additional description of the pts with long-term survival, including updated safety data as well as 3-y OS by smoking history, histology, EGFRstatus, and prior radiation therapy, will be presented. Conclusions: Pembro provides promising long-term OS benefit for 1L and previously treated advanced NSCLC pts expressing PD-L1. The current data represent the longest efficacy and safety follow-up for pts with advanced NSCLC treated with pembro. Clinical trial information: NCT01295827. [Table: see text]


2006 ◽  
Vol 72 (8) ◽  
pp. 5143-5149 ◽  
Author(s):  
Tatiana Rochat ◽  
Jean-Jacques Gratadoux ◽  
Alexandra Gruss ◽  
Gérard Corthier ◽  
Emmanuelle Maguin ◽  
...  

ABSTRACT Lactic acid bacteria (LAB) are generally sensitive to H2O2, a compound that they can paradoxically produce themselves, as is the case for Lactobacillus bulgaricus. Lactobacillus plantarum ATCC 14431 is one of the very few LAB strains able to degrade H2O2 through the action of a nonheme, manganese-dependent catalase (hereafter called MnKat). The MnKat gene was expressed in three catalase-deficient LAB species: L. bulgaricus ATCC 11842, Lactobacillus casei BL23, and Lactococcus lactis MG1363. While the protein could be detected in all heterologous hosts, enzyme activity was observed only in L. casei. This is probably due to the differences in the Mn contents of the cells, which are reportedly similar in L. plantarum and L. casei but at least 10- and 100-fold lower in Lactococcus lactis and L. bulgaricus, respectively. The expression of the MnKat gene in L. casei conferred enhanced oxidative stress resistance, as measured by an increase in the survival rate after exposure to H2O2, and improved long-term survival in aerated cultures. In mixtures of L. casei producing MnKat and L. bulgaricus, L. casei can eliminate H2O2 from the culture medium, thereby protecting both L. casei and L. bulgaricus from its deleterious effects.


2003 ◽  
Vol 39 ◽  
pp. 11-24 ◽  
Author(s):  
Justin V McCarthy

Apoptosis is an evolutionarily conserved process used by multicellular organisms to developmentally regulate cell number or to eliminate cells that are potentially detrimental to the organism. The large diversity of regulators of apoptosis in mammalian cells and their numerous interactions complicate the analysis of their individual functions, particularly in development. The remarkable conservation of apoptotic mechanisms across species has allowed the genetic pathways of apoptosis determined in lower species, such as the nematode Caenorhabditis elegans and the fruitfly Drosophila melanogaster, to act as models for understanding the biology of apoptosis in mammalian cells. Though many components of the apoptotic pathway are conserved between species, the use of additional model organisms has revealed several important differences and supports the use of model organisms in deciphering complex biological processes such as apoptosis.


2002 ◽  
Vol 38 ◽  
pp. 9-19 ◽  
Author(s):  
Guy S Salvesen

The ability of metazoan cells to undergo programmed cell death is vital to both the precise development and long-term survival of the mature adult. Cell deaths that result from engagement of this programme end in apoptosis, the ordered dismantling of the cell that results in its 'silent' demise, in which packaged cell fragments are removed by phagocytosis. This co-ordinated demise is mediated by members of a family of cysteine proteases known as caspases, whose activation follows characteristic apoptotic stimuli, and whose substrates include many proteins, the limited cleavage of which causes the characteristic morphology of apoptosis. In vertebrates, a subset of caspases has evolved to participate in the activation of pro-inflammatory cytokines, and thus members of the caspase family participate in one of two very distinct intracellular signalling pathways.


2000 ◽  
Vol 111 (1) ◽  
pp. 363-370 ◽  
Author(s):  
Katsuto Takenaka ◽  
Mine Harada ◽  
Tomoaki Fujisaki ◽  
Koji Nagafuji ◽  
Shinichi Mizuno ◽  
...  

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