scholarly journals Drug-tolerant idling melanoma cells exhibit theory-predicted metabolic low-low phenotype

2019 ◽  
Author(s):  
Dongya Jia ◽  
B. Bishal Paudel ◽  
Corey E. Hayford ◽  
Keisha N. Hardeman ◽  
Herbert Levine ◽  
...  
Keyword(s):  
Cell Division ◽  
Kinetic Model ◽  
Oxidative Phosphorylation ◽  
Experimental Approach ◽  
Melanoma Cells ◽  
Metabolic Adaptation ◽  
Metabolic Profiles ◽  
Sequencing Data ◽  
Melanoma Treatment

AbstractCancer cells adjust their metabolic profiles to evade treatment. Metabolic adaptation is complex and hence better understood by an integrated theoretical-experimental approach. Using a minimal kinetic model, we predicted a previously undescribed Low/Low (L/L) phenotype, characterized by low oxidative phosphorylation (OXPHOS) and low glycolysis. Here, we report that L/L metabolism is observed in BRAF-mutated melanoma cells that enter a drug-tolerant “idling state” upon long-term MAPK inhibition (MAPKi). Consistently, using publicly available RNA-sequencing data of both cell lines and patient samples, we show that melanoma cells decrease their glycolysis and/or OXPHOS activity upon MAPKi and converge toward the L/L phenotype. L/L metabolism is unfavorable for tumor growth, yet supports successful cell division at ~50% rate. Thus, L/L drug-tolerant idling cells are a reservoir for accumulating mutations responsible for relapse, and it should be considered as a target subpopulation for improving MAPKi outcomes in melanoma treatment.

The effects of chlordane on the green algae Scenedesmus quadricauda and Chlamydomonas sp.

1977 ◽  
Vol 55 (23) ◽  
pp. 2866-2872 ◽  
Author(s):  
Valanne Glooschenko ◽  
John N. A. Lott
Keyword(s):  
Cell Division ◽  
Oxidative Phosphorylation ◽  
Aquatic Ecosystems ◽  
Scenedesmus Quadricauda ◽  
Photosynthetic Response ◽  
Cell Numbers ◽  
Respiration Rates ◽  
Chlamydomonas Sp ◽  
Stimulation Of

Chlordane is an organochlorine soil insecticide whose effects upon aquatic ecosystems, and particularly on algae, are little known. Experimental results indicate that chlordane concentrations ranging from 0.1 to 100 μg/ℓ significantly stimulate cell division of Scenedesmus quadricauda, a common planktonic green alga. Chlordane in concentrations from 0.1 to 50 μg/ℓ is also stimulatory to the growth of Chlamydomonas sp., isolated from soil. However, 100 μg/ℓ was inhibitory to cell division in this species.Significant stimulatory effects on the respiration rates of these two species were observed at all concentrations within 3 to 4 h of chlordane addition. Stimulation of respiration increased with increasing chlordane concentration. Similar stimulatory effects on respiration were produced using 2,4-dinitrophenol (DNP), a known uncoupling agent of oxidative phosphorylation. Long-term inhibition of photosynthetic response of Scenedesmus quadricauda treated with the higher chlordane concentrations was observed over the course of the experiment even though a significant increase in cell numbers over the control was noted. A highly significant chlordane–light interaction was observed on photosynthesis of both S. quadricauda and Chlamydomonas sp.

scholarly journals In-Frame and Frameshift Mutations in Zebrafish presenilin 2 Affect Different Cellular Functions in Young Adult Brains

2021 ◽  
pp. 1-10
Author(s):  
Karissa Barthelson ◽  
Stephen Martin Pederson ◽  
Morgan Newman ◽  
Haowei Jiang ◽  
Michael Lardelli
Keyword(s):  
Cell Cycle ◽  
Young Adult ◽  
Oxidative Phosphorylation ◽  
Frameshift Mutation ◽  
Long Term Potentiation ◽  
Cellular Functions ◽  
Reading Frame ◽  
Term Potentiation ◽  
Presenilin 2

Background: Mutations in PRESENILIN 2 (PSEN2) cause early onset familial Alzheimer’s disease (EOfAD) but their mode of action remains elusive. One consistent observation for all PRESENILIN gene mutations causing EOfAD is that a transcript is produced with a reading frame terminated by the normal stop codon—the “reading frame preservation rule”. Mutations that do not obey this rule do not cause the disease. The reasons for this are debated. Objective: To predict cellular functions affected by heterozygosity for a frameshift, or a reading frame-preserving mutation in zebrafish psen2 using bioinformatic techniques. Methods: A frameshift mutation (psen2N140fs) and a reading frame-preserving (in-frame) mutation (psen2T141 _ L142delinsMISLISV) were previously isolated during genome editing directed at the N140 codon of zebrafish psen2 (equivalent to N141 of human PSEN2). We mated a pair of fish heterozygous for each mutation to generate a family of siblings including wild type and heterozygous mutant genotypes. Transcriptomes from young adult (6 months) brains of these genotypes were analyzed. Results: The in-frame mutation uniquely caused subtle, but statistically significant, changes to expression of genes involved in oxidative phosphorylation, long-term potentiation and the cell cycle. The frameshift mutation uniquely affected genes involved in Notch and MAPK signaling, extracellular matrix receptor interactions and focal adhesion. Both mutations affected ribosomal protein gene expression but in opposite directions. Conclusion: A frameshift and an in-frame mutation at the same position in zebrafish psen2 cause discrete effects. Changes in oxidative phosphorylation, long-term potentiation and the cell cycle may promote EOfAD pathogenesis in humans.

scholarly journals Current Advancements and Novel Strategies in the Treatment of Metastatic Melanoma

2021 ◽  
Vol 20 ◽  
pp. 153473542199007
Author(s):  
Siddhartha Sood ◽  
Rahul Jayachandiran ◽  
Siyaram Pandey
Keyword(s):  
Metastatic Melanoma ◽  
Complementary Therapy ◽  
Natural Health Products ◽  
Combination Therapies ◽  
Natural Health ◽  
The Past ◽  
Health Products ◽  
Melanoma Treatment ◽  
New Research

Melanoma is the deadliest form of skin cancer in the world with a growing incidence in North America. Contemporary treatments for melanoma include surgical resection, chemotherapy, and radiotherapy. However, apart from resection in early melanoma, the prognosis of patients using these treatments is typically poor. In the past decade, there have been significant advancements in melanoma therapies. Immunotherapies such as ipilimumab and targeted therapies such as vemurafenib have emerged as a promising option for patients as seen in both scientific and clinical research. Furthermore, combination therapies are starting to be administered in the form of polychemotherapy, polyimmunotherapy, and biochemotherapy, of which some have shown promising outcomes in relative efficacy and safety due to their multiple targets. Alongside these treatments, new research has been conducted into the evidence-based use of natural health products (NHPs) and natural compounds (NCs) on melanoma which may provide a long-term and non-toxic form of complementary therapy. Nevertheless, there is a limited consolidation of the research conducted in emerging melanoma treatments which may be useful for researchers and clinicians. Thus, this review attempts to evaluate the therapeutic efficacy of current advancements in metastatic melanoma treatment by surveying new research into the molecular and cellular basis of treatments along with their clinical efficacy. In addition, this review aims to elucidate novel strategies that are currently being used and have the potential to be used in the future.

Management problems in the pregnant diabetic

1993 ◽  
Vol 5 (1) ◽  
pp. 29-38 ◽  
Author(s):  
FA Van Assche
Keyword(s):  
Gestational Diabetes ◽  
Pathological Condition ◽  
Metabolic Adaptation ◽  
Medical Complication ◽  
Mother And Child ◽  
Insulin Dependent ◽  
Underlying Mechanisms ◽  
Near Future ◽  
Pregnant Diabetic

Major progress has been made in the knowledge and management of diabetes and pregnancy. However diabetes in pregnancy remains an important medical complication, with implications for mother and child in both the short and the long term. There are still controversies concerning the diagnostic criteria of gestational diabetes and concerning the best strategry for the treatment of this disorder. There is even less agreement about whether gestational diabetes is a pathological condition. The perinatal mortality in gestational diabetes has recently become as low as that in the general population. This has led to the conclusion that gestational diabetes is no more than a variant of metabolic adaptation during pregnancy. However, fetal hyperinsulinism is present in gestational diabetes, resulting in macrosomia, neonatal complications and most probably long term consequences. Improvements in the care of the preexisting insulin-dependent pregnant diabetic have been achieved but further progress in understanding the underlying mechanisms and in preventing and treating the disease are important goals for the near future.

An Experimental Approach to the Function of Classic Maya Chultuns

1971 ◽  
Vol 36 (3) ◽  
pp. 322-335 ◽  
Author(s):  
Dennis E. Puleston
Keyword(s):  
Experimental Approach ◽  
Experimental Studies ◽  
Water Storage ◽  
Food Storage ◽  
Food Crop ◽  
Traditional Foods ◽  
Long Term Storage ◽  
Brosimum Alicastrum ◽  
Term Storage

AbstractExperimental techniques have provided an exciting breakthrough for the functional analysis of Maya chultuns. While deep cistern-like chultuns, common at certain sites in the northern lowlands, have been shown to be functional for water storage, smaller lateral-chambered chultuns characteristic of certain parts of the southern lowlands probably had a very different function. Excavation and examination of the latter features, in light of a whole range of possibilities, suggest that they were constructed to be used for food storage. Experimental studies, however, reveal them to be unsuitable for the storage of most traditional foods, including maize. At least one local food crop, the seed of the ramon (Brosimum alicastrum, Moraceae), appears to be ideally suited for long-term storage under these conditions. Chambers constructed beneath platforms in the northern lowlands may have been used for the storage of maize. A need for more experimental work is indicated.

scholarly journals The Impact of the COVID-19 Pandemic on Antibiotic Prescribing Trends in Outpatient Care: A Nationwide, Quasi-Experimental Approach

Antibiotics ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1040
Author(s):  
Tânia Magalhães Silva ◽  
Marta Estrela ◽  
Eva Rebelo Gomes ◽  
Maria Piñeiro-Lamas ◽  
Adolfo Figueiras ◽  
...  
Keyword(s):  
Public Health ◽  
Outpatient Care ◽  
Experimental Approach ◽  
National Level ◽  
Series Data ◽  
Antibiotic Prescribing ◽  
Prescribing Trends ◽  
Quasi Experimental ◽  
The Impact

Coronavirus disease 2019 (COVID-19) has spread globally and is currently having a damaging impact on nearly all countries in the world. The implementation of stringent measures to stop COVID-19 dissemination had an influence on healthcare services and associated procedures, possibly causing antibiotic consumption fluctuations. This paper aims to evaluate the immediate and long-term impact of the COVID-19 pandemic on antibiotic prescribing trends in outpatient care of the Portuguese public health sector, including in primary healthcare centers and hospitals, as well as on specific antibiotic groups known to be closely associated with increased resistance. Segmented regression analysis with interrupted time series data was used to analyze whether the COVID-19 pandemic had an impact in antibiotic prescribing tendencies at a national level. The outcomes from this quasi-experimental approach demonstrate that, at the beginning of the pandemic, a significant, immediate decrease in the overall antibiotic prescribing trends was noticed in the context of outpatient care in Portugal, followed by a statistically non-significant fall over the long term. The data also showed a significant reduction in the prescription of particular antibiotic classes (antibiotics from the Watch group, 3rd-generation cephalosporins, fluoroquinolones, and clarithromycin) upon COVID-19 emergence. These findings revealed an important disruption in antibiotics prescribing caused by the current public health emergency.

scholarly journals A Novel Distinct Genetic Variant of Tomato Torrado Virus with Substantially Shorter RNA1-Specific 3’untranslated Region (3’UTR)

Plants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2454
Author(s):  
Marta Budziszewska ◽  
Przemysław Wieczorek
Keyword(s):  
Amino Acid ◽  
Genetic Variability ◽  
Untranslated Region ◽  
Genetic Variant ◽  
Sequencing Data ◽  
Sequence Analyses ◽  
Nucleotide Substitutions ◽  
Systemic Necrosis ◽  
Single Nucleotide

Tomato torrado virus (ToTV) induces severe systemic necrosis in Solanum lycopersicum. This work aimed at describing the genetic variability of necrosis-inducing ToTV-Wal’17 collected in 2017, derived from the ToTV-Wal’03 after long-term passages in plants. Sequence analyses of the ToTV-Wal’17 indicated twenty-eight single nucleotide substitutions in coding sequence of both RNAs, twelve of which resulted in amino acid changes in viral polyproteins. Moreover the sequencing data revealed that the 3’UTR of ToTV-Wal’17 RNA1 was 394 nts shorter in comparison to Wal’03. The performed sequence analyses revealed that 3’UTR of RNA1 of ToTV-Wal’17 is the most divergent across all previously described European isolates.

scholarly journals Energy Expenditure, Fat Oxidation, and Body Weight Regulation: A Study of Metabolic Adaptation to Long- Term Weight Change

2000 ◽  
Vol 85 (3) ◽  
pp. 1087-1094 ◽  
Author(s):  
Christian Weyer ◽  
Richard E. Pratley ◽  
Arline D. Salbe ◽  
Clifton Bogardus ◽  
Eric Ravussin ◽  
...  
Keyword(s):  
Body Weight ◽  
Energy Expenditure ◽  
Weight Change ◽  
Fat Oxidation ◽  
Metabolic Adaptation ◽  
Weight Regulation ◽  
Body Weight Regulation
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