scholarly journals Harnessing Lactate Metabolism for Radiosensitization

2021 ◽  
Vol 11 ◽  
Author(s):  
Kevin X. Liu ◽  
Emily Everdell ◽  
Sharmistha Pal ◽  
Daphne A. Haas-Kogan ◽  
Michael G. Milligan
Keyword(s):  
Lactate Dehydrogenase ◽  
Lipid Synthesis ◽  
Monocarboxylate Transporters ◽  
Future Research ◽  
Lactate Metabolism ◽  
Clinical Safety ◽  
Promote Cell Proliferation ◽  
Downstream Effects ◽  
Mitochondrial Pyruvate Carrier ◽  
Immunosuppressive Tumor Microenvironment

Cancer cells rewire their metabolism to promote cell proliferation, invasion, and metastasis. Alterations in the lactate pathway have been characterized in diverse cancers, correlate with outcomes, and lead to many downstream effects, including decreasing oxidative stress, promoting an immunosuppressive tumor microenvironment, lipid synthesis, and building chemo- or radio-resistance. Radiotherapy is a key modality of treatment for many cancers and approximately 50% of patients with cancer will receive radiation for cure or palliation; thus, overcoming radio-resistance is important for improving outcomes. Growing research suggests that important molecular controls of the lactate pathway may serve as novel therapeutic targets and in particular, radiosensitizers. In this mini-review, we will provide an overview of lactate metabolism in cancer, discuss three important contributors to lactate metabolism (lactate dehydrogenase, monocarboxylate transporters, and mitochondrial pyruvate carrier), and present data that inhibition of these three pathways can lead to radiosensitization. Future research is needed to further understand critical regulators of lactate metabolism and explore clinical safety and efficacy of inhibitors of lactate dehydrogenase, monocarboxylate transporters, and mitochondrial pyruvate carrier alone and in combination with radiation.

scholarly journals Lactate metabolism in strictly anaerobic microorganisms with a soluble NAD + ‐dependent L‐lactate dehydrogenase

2021 ◽  
Author(s):  
Florian P. Rosenbaum ◽  
Anja Poehlein ◽  
Richard Egelkamp ◽  
Rolf Daniel ◽  
Sönke Harder ◽  
...  
Keyword(s):  
Lactate Dehydrogenase ◽  
Strictly Anaerobic ◽  
Lactate Metabolism ◽  
Anaerobic Microorganisms

scholarly journals Ketamine’s effect on inflammation and kynurenine pathway in depression: A systematic review

2021 ◽  
pp. 026988112110264
Author(s):  
Emma Kopra ◽  
Valeria Mondelli ◽  
Carmine Pariante ◽  
Naghmeh Nikkheslat
Keyword(s):  
Systematic Review ◽  
Animal Studies ◽  
Bipolar Depression ◽  
Strong Support ◽  
Kynurenine Pathway ◽  
Future Research ◽  
Downstream Effects ◽  
Tnf Α ◽  
The Central Nervous System ◽  
Anti Inflammatory

Background: Ketamine is a novel rapid-acting antidepressant with high efficacy in treatment-resistant patients. Its exact therapeutic mechanisms of action are unclear; however, in recent years its anti-inflammatory properties and subsequent downstream effects on tryptophan (TRP) metabolism have sparked research interest. Aim: This systematic review examined the effect of ketamine on inflammatory markers and TRP–kynurenine (KYN) pathway metabolites in patients with unipolar and bipolar depression and in animal models of depression. Methods: MEDLINE, Embase, and PsycINFO databases were searched on October 2020 (1806 to 2020). Results: Out of 807 initial results, nine human studies and 22 animal studies on rodents met the inclusion criteria. Rodent studies provided strong support for ketamine-induced decreases in pro-inflammatory cytokines, namely in interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α and indicated anti-inflammatory effects on TRP metabolism, including decreases in the enzyme indoleamine 2,3-dioxygenase (IDO). Clinical evidence was less robust with high heterogeneity between sample characteristics, but most experiments demonstrated decreases in peripheral inflammation including in IL-1β, IL-6, and TNF-α. Preliminary support was also found for reduced activation of the neurotoxic arm of the KYN pathway. Conclusion: Ketamine appears to induce anti-inflammatory effects in at least a proportion of depressed patients. Suggestions for future research include investigation of markers in the central nervous system and examination of clinical relevance of inflammatory changes.

scholarly journals Synchronicity of Signage

2018 ◽  
Vol 2 (2) ◽  
pp. 30-40
Author(s):  
Dawn Jourdan ◽  
Aparna Sundar ◽  
Flavia Igliori Gonsales ◽  
Gracie Schaefer
Keyword(s):  
Sense Of Belonging ◽  
Future Research ◽  
Downstream Effects ◽  
Consumer Inferences

The role of synchronicity in signage is investigated in three studies. Synchronicity has been theoretically linked to solidarity or a feeling of unity. In this research, we empirically investigate the effects of depicting synchronicity in signage, using the visual principle of rhythm. Rhythm of the imagery as synchronicity in signage increases entitativity and a sense of belonging. We demonstrate key downstream effects that can be leveraged in shaping consumer inferences in community and commercial contexts. Finally, we demonstrate the effectiveness of this strategy, but only when prior perceptions of belongingness are absent. Implications for theory and future research are discussed.

scholarly journals Myelin Fat Facts: An Overview of Lipids and Fatty Acid Metabolism

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 812 ◽  
Author(s):  
Yannick Poitelon ◽  
Ashley M. Kopec ◽  
Sophie Belin
Keyword(s):  
Fatty Acids ◽  
Nervous System ◽  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Lipid Synthesis ◽  
The Body ◽  
Proper Function ◽  
Future Research ◽  
Basic Biology

Myelin is critical for the proper function of the nervous system and one of the most complex cell–cell interactions of the body. Myelination allows for the rapid conduction of action potentials along axonal fibers and provides physical and trophic support to neurons. Myelin contains a high content of lipids, and the formation of the myelin sheath requires high levels of fatty acid and lipid synthesis, together with uptake of extracellular fatty acids. Recent studies have further advanced our understanding of the metabolism and functions of myelin fatty acids and lipids. In this review, we present an overview of the basic biology of myelin lipids and recent insights on the regulation of fatty acid metabolism and functions in myelinating cells. In addition, this review may serve to provide a foundation for future research characterizing the role of fatty acids and lipids in myelin biology and metabolic disorders affecting the central and peripheral nervous system.

Phosphotyrosine-containing lactate dehydrogenase is restricted to the nuclei of PC12 pheochromocytoma cells

1990 ◽  
Vol 10 (2) ◽  
pp. 770-776
Author(s):  
X H Zhong ◽  
B D Howard
Keyword(s):  
Lactate Dehydrogenase ◽  
Cell Transformation ◽  
Lactate Metabolism ◽  
Wild Type ◽  
Altered Expression ◽  
Pheochromocytoma Cells ◽  
Ldh Isoenzymes ◽  
Tumor Viruses ◽  
A Subunit ◽  
Pc12 Pheochromocytoma Cells

There are five lactate dehydrogenase (LDH) isoenzymes, composed of various combinations of two types of subunits. LDH-5, which contains only the LDH A subunit, is known to be present in both the cytoplasm and the nucleus, to act as a single-stranded DNA-binding protein possibly functioning in transcription and/or replication, and to undergo phosphorylation of tyrosine 238 in approximately 1% of the enzyme after cell transformation by certain tumor viruses. We have characterized LDH from wild-type PC12 pheochromocytoma cells and from a PC12 variant (MPT1) that exhibits altered lactate metabolism and altered expression of multiple genes. Wild-type and MPT1 cells contain different proportions of LDH isoenzymes, with LDH-5 being more predominant in wild-type cells than in the variant. A small fraction of LDH from PC12 cells contains phosphotyrosine. Approximately 99% of the total LDH activity is located in the cytoplasm, but all of the phosphotyrosine-containing LDH is located in the nucleus. Furthermore, essentially all of the nuclear LDH contains phosphotyrosine. These results suggest that tyrosine phosphorylation can affect its role in the nucleus.

The impact of varying warning color on e-cigarette advertisements: Results from an online experiment among young adults

2021 ◽  
Author(s):  
Jessica L King ◽  
Connor Simper ◽  
Jacob Razzouk ◽  
Julie W Merten
Keyword(s):  
Young Adults ◽  
Tobacco Use ◽  
Future Research ◽  
White Background ◽  
Chi Square ◽  
Message Effectiveness ◽  
Black And White ◽  
Black Background ◽  
Downstream Effects ◽  
The Impact

Abstract Introduction Advertisement warnings are often overlooked, which reduces the opportunity for risk communication. Methods We used Prolific to survey 1,131 young adults (18-35) who currently used e-cigarettes or tobacco products. We randomized participants to one of four warning conditions: black text on white background (BW), white on black (WB), black on yellow (BY), and yellow on black (YB). We examined associations between condition and attention, recall, ad appeal, perceived message effectiveness (PME), and intentions to use e-cigarettes using chi-square and ANOVA where appropriate. We conducted logistic regressions by condition for attention and recall controlling for demographics and tobacco use. Results The warning was selected as the most attention-capturing area of the advertisement more often by those exposed to yellow warnings than white (59.9% versus 46.8%), even after controlling for demographics and tobacco use (p<.05). Recall was greater among those exposed to yellow warnings than white (44.2% vs. 37.3%), which held in controlled models. There were no significant differences between yellow and white warnings for ad appeals, PME, or intentions to use. In subanalyses, WB warnings generated higher PME (10.1 vs. 9.5) and lower intentions to use e-cigarettes (3.0 vs. 3.3) than BW (each p<.05). Conclusions Yellow warning color increases attention and recall of the warning, but this increase in attention did not translate to differences in downstream effects. Among currently mandated warning variations, the white text on black background warning appears more effective than the black on white. Future research should examine whether differences translate to behavior change. Implications We tested color variations of the FDA-mandated nicotine text warning on e-cigarette advertisements. Yellow variations (yellow text on black background and black on yellow) better captured attention and increased warning recall compared to the mandated black and white warnings. Among the FDA-mandated black on white and white on black warnings, the white on black variation appears more effective, generating higher perceived message effectiveness and lower intentions to use e-cigarettes. Given the difficulty in implementing pictorial warnings in the US, color might represent an alternative to improve warning effectiveness. Findings may also be applicable to those designing tobacco-related health communications.

The Psychology of Status Competitions within Organizations

2021 ◽  
Author(s):  
Sarah P. Doyle ◽  
Sijun Kim ◽  
Hee Young Kim
Keyword(s):  
Behavioral Outcomes ◽  
Future Research ◽  
Individual Outcomes ◽  
Downstream Effects ◽  
Status Seeking ◽  
Group Members

Status hierarchies, which represent how individuals stack up based on the amount of influence and respect they have relative to others, develop quickly as group members make judgments and inferences about others’ competencies or expected contributions to the group. While quick to emerge, one’s place in the hierarchy is not entirely fixed. Because occupying higher status offers a number of rewards and benefits, people vie with others to achieve the higher status positions, and seek to maintain them by engaging in behaviors that have downstream effects on group and individual outcomes. Scholars have directed increasing attention to the unique psychology associated with status seeking to understand the consequences of hierarchical competitions. This emerging body of work highlights the dual concerns (i.e., self-oriented and other-oriented concerns) inherent in the pursuit of status and offers new insights to aid our understanding of status competitions. In this chapter, the authors first review the literature that explores the mixed-motive psychology of status striving, noting the potentially beneficial and destructive behavioral outcomes that status competitions can elicit within workgroups. Next, the authors detail some of the structural, temporal, relational, and individual properties that may exacerbate people’s self-interested status concerns. The chapter concludes by discussing some of the organizational implications of this body of work and reviewing potentially rich opportunities for future research on status competitions.

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