The role of desaturases in cold-induced lipid restructuring

2002 ◽  
Vol 30 (6) ◽  
pp. 1082-1086 ◽  
Author(s):  
A. R. Cossins ◽  
P. A. Murray ◽  
A. Y. Gracey ◽  
J. Logue ◽  
S. Polley ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Unsaturated Fatty Acids ◽  
Physical Structure ◽  
Head Group ◽  
Adaptive Responses ◽  
Membrane Phospholipids ◽  
The Face ◽  
Liver Membranes ◽  
Translational Mechanisms

All organisms respond to environmental challenge by adaptive responses, although, in many cases, the underlying molecular mechanisms are not understood. In the case of membranes, the physical structure of membrane phospholipids is conserved in the face of cold, rigidifying conditions by the elevated proportions of unsaturated fatty acids. We have observed a clear positional specificity in this substitution and head group preferences in carp liver membranes. We have also demonstrated changes in the activity of lipid desaturases that mediate the unsaturation response, caused by both transcriptional and post-translational mechanisms. Another hepatic isoform has recently been discovered with sensitivity, not to cooling, but to dietary variations. Finally, we are testing the importance of desaturase inductions in the inducible cold tolerance of the whole animal.

scholarly journals ER stress and development of type 1 diabetes

2016 ◽  
Vol 64 (1) ◽  
pp. 2-6 ◽  
Author(s):  
Feyza Engin
Keyword(s):  
Type 1 Diabetes ◽  
Er Stress ◽  
Molecular Mechanisms ◽  
Adaptive Responses ◽  
Β Cell ◽  
Cellular Homeostasis ◽  
Unfolded Protein

Type 1 diabetes (T1D) results from an autoimmune-mediated destruction of pancreatic β cells. The incidence of T1D is on the rise globally around 3% to 5% per year and rapidly increasing incidence in younger children is of the greatest concern. currently, there is no way to cure or prevent T1D; hence, a deeper understanding of the underlying molecular mechanisms of this disease is essential to the development of new effective therapies. The endoplasmic reticulum (ER) is an organelle with multiple functions that are essential for cellular homeostasis. Excessive demand on the ER, chronic inflammation, and environmental factors lead to ER stress and to re-establish cellular homeostasis, the adaptive unfolded protein response (UPR) is triggered. However, chronic ER stress leads to a switch from a prosurvival to a proapoptotic UPR, resulting in cell death. Accumulating data have implicated ER stress and defective UPR in the pathogenesis of inflammatory and autoimmune diseases, and ER stress has been implicated in β-cell failure in type 2 diabetes. However, the role of ER stress and the UPR in β-cell pathophysiology and in the initiation and propagation of the autoimmune responses in T1D remains undefined. This review will highlight the current understanding and recent in vivo data on the role of ER stress and adaptive responses in T1D pathogenesis and the potential therapeutic aspect of enhancing β-cell ER function and restoring UPR defects as novel clinical strategies against this disease.

Contextualizing the Popol Wuj from Friar Ximénez to the Digital Age

2018 ◽  
Author(s):  
Néstor Quiroa
Keyword(s):  
Oral History ◽  
18Th Century ◽  
Physical Structure ◽  
Cultural Continuity ◽  
Electronic Information ◽  
Cultural Contact ◽  
Indigenous Groups ◽  
The Face ◽  
Historical Trajectory

Regarded as an ethnohistorical treasure, the Popol Wuj narrative has been read exclusively as a freestanding, self-contained text used to inquire into a history far removed from when it was actually created. Consequently, the colonial context of the text itself has been minimized, including the central role of Dominican friar Francisco Ximénez as transcriber and translator of the only copy in existence. The present study delineates a historical trajectory of the Popol Wuj, reframing the narrative within its colonial ecclesiastic context. It explores the physical structure of Friar Ximénez’s 18th-century manuscript, preserved as MS 1515 by the Newberry Library in Chicago, to demonstrate that his work was first and foremost a series of religious treatises intended to carry out the conversion of the K’iche’ to Christianity. As a cautionary word, rather than revisiting the old, biased approach of questioning the authenticity and authorship of this Popol Wuj narrative, the current study suggests a broader reading, addressing the complexities intrinsic in this text, particularly the fact that the narrative was the result of the cultural contact between mendicant friars, whose main objective was to evangelize, and indigenous groups, who strived to maintain their cultural continuity by recording their oral history in the face of such a threat. Finally, this study invites scholars to ponder on the implications that the present structure of Ximénez’s manuscript (MS 1515) presents for future Popol Wuj studies as the narrative enters the age of electronic information and digital imaging.

Regulation Of The Fatty Acid Composition Of Platelet Phospholipids

1981 ◽  
Author(s):  
M L McKean ◽  
J B Smith ◽  
M J Silver
Keyword(s):  
Fatty Acids ◽  
Fatty Acid Composition ◽  
Fatty Acid ◽  
Acid Composition ◽  
Unsaturated Fatty Acids ◽  
De Novo ◽  
Membrane Phospholipids ◽  
De Novo Biosynthesis ◽  
Coa Transferase

The fatty acid composition of cell membrane phospholipids does not remain constant after de novo biosynthesis, but undergoes continual remodelling. One of the major routes for remodelling probably includes the deacylation-reacylation steps of the Lands Pathway. This has been shown to be important for the incorporation of long chain, polyunsaturated fatty acids into phospholipids by liver and brain. An understanding of the mechanisms involved in these processes in platelets is especially important in light of the large stores of arachidonic acid (AA) in platelet phospholipids and the role of AA in hemostasis and thrombosis. Previous results from this laboratory have shown that the turnover of radioactive AA, 8,11,14-eicosatrienoic and 5,8,11,14,17-eicosapentaenoic acids in the phospholipids of resting platelets is more rapid than the turnover of radioactive C16 and C18 saturated and unsaturated fatty acids. However, little is known about how fatty acids, especially AA and its homologues, are incorporated into platelet phospholipids during de novo biosynthesis or how they are exchanged during remodelling.At least three enzymes are involved in the deacylation- reacylation of phospholipids: phospholipase A2; acyl CoA synthetase; and acyl CoA transferase. We have studied acyl CoA transferase and have found considerable activity in human platelet membranes. Experiments are in progress to determine the substrate specificity and other properties of this enzyme.

scholarly journals The role of FLOWERING LOCUS C in vernalization of Brassica: the importance of vernalization research in the face of climate change

2018 ◽  
Vol 69 (1) ◽  
pp. 30 ◽  
Author(s):  
Daniel J. Shea ◽  
Etsuko Itabashi ◽  
Satoko Takada ◽  
Eigo Fukai ◽  
Tomohiro Kakizaki ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Model Organism ◽  
Climatic Changes ◽  
Environmental Cues ◽  
Plant Responses ◽  
Agricultural Crops ◽  
Regulatory Pathways ◽  
Evolutionarily Conserved ◽  
The Face

As climatic changes occur over the coming decades, our scientific understanding of plant responses to environmental cues will become an increasingly important consideration in the breeding of agricultural crops. This review provides a summary of the literature regarding vernalization research in Brassicaceae, covering both the historical origins of vernalization research and current understanding of the molecular mechanisms behind the regulatory pathways involved in vernalization and subsequent inflorescence. We discuss the evolutionarily conserved biology between the model organism Arabidopsis thaliana and the Brassica genus of crop cultivars and contrast the differences between the genera to illustrate the importance of Brassica-specific research into vernalization.

scholarly journals Epigenetic Influences on Plant Responses to the Environment [University of Wisconsin - Oshkosh]

2019 ◽  
Author(s):  
Angela L Vickman ◽  
Travis Smith ◽  
Hayley Vandenboom ◽  
Lisa A. Dorn
Keyword(s):  
Gene Expression ◽  
Phenotypic Plasticity ◽  
Molecular Mechanisms ◽  
Molecular Level ◽  
Physical Structure ◽  
Plant Responses ◽  
Appropriate Behavior ◽  
Stressful Environment ◽  
University Of Wisconsin

Plants and animals may respond to changes in the environment at the molecular level by changing the amount of a gene product (a protein) to generate the appropriate behavior or physical structure (a phenotype) for that environment. For example, an extremely stressful environment can cause plants to reproduce immediately rather than waiting for conditions to improve. The molecular mechanisms for changing phenotype with environment (phenotypic plasticity) are not clear, however previous studies have shown plasticity may be the result of failing to change expression to maintain a phenotype or a deliberate change in expression altering the phenotype. To explore the molecular mechanisms underlying phenotypic plasticity, I am using a minION sequencing apparatus to re-sequence three inbred lines of Arabidopsis thaliana with extreme phenotypic plasticity differences and gene expression differences with the environment. I will specifically explore the role of methylated cytosines and adenines in gene expression.

scholarly journals Ionpair-π interactions favor cell penetration of arginine/tryptophan-rich cell-penetrating peptides

2019 ◽  
Author(s):  
Astrid Walrant ◽  
Antonio Bauzá ◽  
Claudia Girardet ◽  
Isabel D. Alves ◽  
Sophie Lecomte ◽  
...  
Keyword(s):  
Lipid Bilayers ◽  
Density Functional ◽  
Molecular Mechanisms ◽  
Cell Penetrating Peptides ◽  
Membrane Phospholipids ◽  
Active Peptides ◽  
Π Interactions ◽  
Cell Penetrating ◽  
Membrane Active Peptides

AbstractCell-penetrating peptides (CPPs) internalization can occur both by endocytosis and direct translocation through the cell membrane. These different entry routes suggest that molecular partners at the plasma membrane, phospholipids or glycosaminoglycans (GAGs), bind CPPs with different affinity or selectivity. The analysis of sequence-dependent interactions of CPPs with lipids and GAGs should lead to a better understanding of the molecular mechanisms underlying their internalization. CPPs are short sequences generally containing a high number of basic arginines and lysines and sometimes aromatic residues, in particular tryptophans. Tryptophans are crucial residues in membrane-active peptides, because they are important for membrane interaction. Membrane-active peptides often present facial amphiphilicity, which also promote the interaction with lipid bilayers. To study the role of Trp and facial amphiphilicity in cell interaction and penetration of CPPs, a nonapeptide series containing only Arg, Trp or D-Trp residues at different positions was designed. Our quantitative study indicates that to maintain/increase the uptake efficiency, Arg can be advantageously replaced by Trp in the nonapeptides. The presence of Trp in oligoarginines increases the uptake in cells expressing GAGs at their surface, when it only compensates for the loss of Arg and maintains similar peptide uptake in GAG-deficient cells. In addition, we show that facial amphiphilicity is not required for efficient uptake of these nonapeptides. Thermodynamic analyses point towards a key role of Trp that highly contributes to the binding enthalpy of complexes formation. Density functional theory (DFT) analysis highlights that salt bridge-π interactions play a crucial role for the GAG-dependent entry mechanisms.

scholarly journals Polar-group behaviour in mixed monolayers of phospholipids and fusogenic lipids

1976 ◽  
Vol 155 (2) ◽  
pp. 353-364 ◽  
Author(s):  
B Maggio ◽  
J A. Lucy
Keyword(s):  
Head Group ◽  
Polar Group ◽  
Membrane Phospholipids ◽  
Molecular Area ◽  
Mixed Monolayers ◽  
Group Behaviour ◽  
Bivalent Cations ◽  
Observed Behaviour ◽  
Glycerol Mono

1. The surface potentials of mixed monolayers of synthetic phospholipids with lipids that are fusogenic for hen erythrocytes were investigated. 2. At pH 5.6 and 10, but not at pH2, mixed monolayers of the fusogenic lipid, glycerol mono-oleate, with phosphatidylcholine exhibited negative deviations from the ideality rule in surface potential per molecule which were accompanied by negative deviations in mean molecular area. 3. Interactions of this type were not seen with chemically related but non-fusogenic lipids, nor were they found in mixed monolayers of any of the lipids with phosphatidylethanolamine. 4. Experiments with dihexadecyl phosphate and hexadecyltrimethyl-ammonium indicated that the complete head group of phosphatidylcholine is required for its observed behaviour with fusogenic lipids. 5. Bivalent cations (Ca2+, UO2(2+) or Zn2+) in the subphase at pH 5.6 significantly modified the behaviour of mixed monolayers of fusogenic lipids with phospholipids; there was a parallel perturbing effect of fusogenic lipids on interactions between monolayers of phospholipids and bivalent cations. 6. Possible molecular interactions of fusogenic lipids with membrane phospholipids, and the role of Ca2+, are discussed which may be relevant to cell fusion in erythrocytes induced by low-melting lipids in the presence of Ca2+.

scholarly journals Rfx6 promotes the differentiation of peptide-secreting enteroendocrine cells while repressing genetic programs controlling serotonin production

2019 ◽  
Author(s):  
Julie Piccand ◽  
Constance Vagne ◽  
Florence Blot ◽  
Aline Meunier ◽  
Anthony Beucher ◽  
...  
Keyword(s):  
Single Cell ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Pancreatic Beta Cell ◽  
Neonatal Diabetes ◽  
Enteroendocrine Cells ◽  
Rna Seq ◽  
Adaptive Responses ◽  
Mouse Intestine

ABSTRACTObjectiveEnteroendocrine cells (EECs) of the gastro-intestinal tract sense gut luminal factors and release peptide hormones or serotonin (5-HT) to coordinate energy uptake and storage. Our goal is to decipher the gene regulatory networks controlling EECs specification from enteroendocrine progenitors. In this context, we studied the role of the transcription factor Rfx6 which had been identified as the cause of Mitchell-Riley syndrome characterized by neonatal diabetes and congenital malabsorptive diarrhea. We previously reported that Rfx6 was essential for pancreatic beta cell development and function, however, the role of Rfx6 in EECs differentiation remained to be elucidated.MethodsWe examined the molecular, cellular and metabolic consequences of constitutive and conditional deletion of Rfx6 in the embryonic and adult mouse intestine. We performed single cell and bulk RNA-Seq to characterize EECs diversity and identify Rfx6-regulated genes.ResultsRfx6 is expressed in the gut endoderm; later it is turned on in, and restricted to, enteroendocrine progenitors and persists in hormone-positive EECs. In the embryonic intestine, the constitutive lack of Rfx6 leads to gastric heterotopia, suggesting a role in the maintenance of intestinal identity. In the absence of intestinal Rfx6, EECs differentiation is severely impaired both in the embryo and adult. However, the number of serotonin-producing enterochromaffin cells and mucosal 5-HT content are increased. Concomitantly, Neurog3-positive enteroendocrine progenitors accumulate. Combined analysis of single-cell and bulk RNA-Seq data revealed that enteroendocrine progenitors differentiate in two main cell trajectories, the enterochromaffin (EC) cells and the Peptidergic Enteroendocrine (PE) cells, whose differentiation programs are differentially regulated by Rfx6. Rfx6 operates upstream of Arx, Pax6 and Isl1 to trigger the differentiation of peptidergic EECs such as GIP-, GLP-1- or CCK-secreting cells. On the contrary, Rfx6 represses Lmx1a and Tph1, two genes essential for serotonin biosynthesis. Finally, we identified transcriptional changes uncovering adaptive responses to the prolonged lack of enteroendocrine hormones and leading to malabsorption and lower food efficiency ratio in Rfx6-deficient mouse intestine.ConclusionThese studies identify Rfx6 as an essential transcriptional regulator of EECs specification and shed light on the molecular mechanisms of intestinal failures in human RFX6-deficiencies such as Mitchell-Riley syndrome.

Role of CPEB-Family Proteins in Memory

2020 ◽  
Author(s):  
Kausik Si
Keyword(s):  
Molecular Mechanisms ◽  
Family Members ◽  
Long Term Memory ◽  
Cytoplasmic Polyadenylation ◽  
Element Binding Protein ◽  
The Face ◽  
Specific Mrnas ◽  
Over Time

A synapse-based mechanism of formation and persistence of long-term memory (LTM) entails some unique mechanistic challenges. It requires experience-dependent changes in synapse composition, function, and number. These changes must be specific to the synapse of interest, although all synapses in a neuron rely on the same genome. Finally, these changes must persist over time in the face of constant synaptic protein turnover. It has long been known that translation at the synapse is one of the fundamental requirements for LTM, and multiple mechanisms of synaptic translation have been characterized. Among these translation regulatory mechanisms, cytoplasmic polyadenylation element binding protein (CPEB) family members fulfill some of the unique needs of LTM and can even be considered as contributing to the biochemical substrates of memory. These proteins orchestrate a “synaptic mark” and regulate translation of specific mRNAs required for changes in synaptic composition, function, and number. Some CPEB family members also self-assemble and alter their function to maintain the altered synaptic state over time, contributing to persistence of memory. This chapter summarizes the known function of different CPEB family members in memory, their underlying molecular mechanisms, and important issues that remain to be resolved.

scholarly journals The role of the hypothalamic-pituitary-adrenal axis in neuroendocrine responses to stress

2006 ◽  
Vol 8 (4) ◽  
pp. 383-395 ◽  
Keyword(s):  
Stress Response ◽  
Brain Stem ◽  
Hpa Axis ◽  
Feedback Inhibition ◽  
Adaptive Responses ◽  
Hypothalamic Pituitary Adrenal ◽  
Afferent Projections ◽  
The Face ◽  
Response To Stress

Animals respond to stress by activating a wide array of behavioral and physiological responses that are collectively referred to as the stress response. Corticotropin-releasing factor (CRF) plays a central role in the stress response by regulating the hypothalamic-pituitary-adrenal (HPA) axis. In response to stress, CRF initiates a cascade of events that culminate in the release of glucocorticoids from the adrenal cortex. As a result of the great number of physiological and behavioral effects exerted by glucocorticoids, several mechanisms have evolved to control HPA axis activation and integrate the stress response. Glucocorticoid feedback inhibition plays a prominent role in regulating the magnitude and duration of glucocorticoid release. In addition to glucocorticoid feedback, the HPA axis is regulated at the level of the hypothalamus by a diverse group of afferent projections from limbic, midbrain, and brain stem nuclei. The stress response is also mediated in part by brain stem noradrenergic neurons, sympathetic andrenomedullary circuits, and parasympathetic systems. In summary, the aim of this review is to discuss the role of the HPA axis in the integration of adaptive responses to stress. We also identify and briefly describe the major neuronal and endocrine systems that contribute to the regulation of the HPA axis and the maintenance of homeostasis in the face of aversive stimuli.

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