Salt-free catanionic systems based on fatty acids exhibit a broad polymorphism by simply tuning the molar ratio between the two components. For fatty acid combined with organic amino counter-ions, very few data are available on the phase... more
Salt-free catanionic systems based on fatty acids exhibit a broad polymorphism by simply tuning the molar ratio between the two components. For fatty acid combined with organic amino counter-ions, very few data are available on the phase behavior obtained as a function of the molar ratio between the counter-ion and the fatty acid. We investigated the choline hydroxide/myristic acid system by varying the molar ratio, R=ncholine hydroxide/nmyristic acid, and the temperature. Myristic acid ionization state was determined by coupling pH, conductivity and infra-red spectroscopy measurements. Self-assemblies were characterized by small angle neutron scattering and microscopy experiments. Self-assembly thermal behavior was investigated by differential scanning calorimetry, wide angle X-ray scattering and nuclear magnetic resonance. For R<1, ionized and protonated myristic acid molecules coexisted leading to the formation of facetted self-assemblies and lamellar phases. The melting proce...
The production of recombinant therapeutic proteins is one of the fastest growing sectors of the pharmaceutical industry, particularly monoclonal antibodies and Fc-fusion proteins. Currently, mammalian cells are the dominant production... more
The production of recombinant therapeutic proteins is one of the fastest growing sectors of the pharmaceutical industry, particularly monoclonal antibodies and Fc-fusion proteins. Currently, mammalian cells are the dominant production system for these proteins because they can perform complex post-translational modifications that are often required for efficient secretion, drug efficacy, and stability. These protein modifications include misfolding and aggregation, oxidation of methionine, deamidation of asparagine and glutamine, variable glycosylation, and proteolysis. Such modifications not only pose challenges for accurate and consistent bioprocessing, but also may have consequences for the patient in that incorrect modifications and aggregation can lead to an immune response to the therapeutic protein. This mini-review describes examples analytical and preventative advances in the fields of protein oxidation, deamidation, misfolding and aggregation (glycosylation is covered in other articles in this issue). The feasibility of partially replacing traditional analytical methods such as peptide mapping with high-throughput screens and their use in clone and media selection are evaluated. This review also discusses how further technical advances could improve the manufacturability, potency, and safety of biotherapeutics.
This report addresses the safety of the inorganic salts and esters of various fatty alcohols of myristic acid. Most of the esters are used as skin conditioning agents in many types of cosmetics in a range of concentrations. Myristate... more
This report addresses the safety of the inorganic salts and esters of various fatty alcohols of myristic acid. Most of the esters are used as skin conditioning agents in many types of cosmetics in a range of concentrations. Myristate esters are readily hydrolyzed to the corresponding alcohols and acids, which are then further metabolized. Myristate salts readily dissociate in any likely cosmetic formulation. The Cosmetic Ingredient Review (CIR) Panel recognized that much of the data supporting the ingredients in this group were previously reviewed in safety assessments for related ingredients. Where specific data did not exist, the Panel considered structure—activity relationships in determining the safety of these ingredients as used in cosmetics. The Panel determined that myristic acid and its salts and esters are safe as cosmetic ingredients in the current practices of use and concentration.
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and depression are considered to be neuro-immune disorders (Maes and Twisk, BMC Medicine 8:35, 2010). There is also evidence that depression and ME/CFS are accompanied by... more
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and depression are considered to be neuro-immune disorders (Maes and Twisk, BMC Medicine 8:35, 2010). There is also evidence that depression and ME/CFS are accompanied by oxidative and nitrosative stress (O&NS) and by increased autoantibodies to a number of self-epitopes some of which have become immunogenic due to damage by O&NS. The aim of this study is to examine IgM-mediated autoimmune responses to different self-epitopes in ME/CFS versus depression. We examined serum IgM antibodies to three anchorage molecules (palmitic and myristic acid and S-farnesyl-L-cysteine); acetylcholine; and conjugated NO-modified adducts in 26 patients with major depression; 16 patients with ME/CFS, 15 with chronic fatigue; and 17 normal controls. Severity of fatigue and physio-somatic (F&S) symptoms was measured with the Fibromyalgia and Chronic Fatigue Syndrome Rating Scale. Serum IgM antibodies to the three anchorage molecules and NO-phenylalanine were significantly higher in ME/CFS than in depression. The autoimmune responses to oxidatively, but not nitrosatively, modified self-epitopes were significantly higher in ME/CFS than in depression and were associated with F&S symptoms. The autoimmune activity directed against conjugated acetylcholine did not differ significantly between ME/CFS and depression, but was greater in the patients than controls. Partially overlapping pathways, i.e. increased IgM antibodies to a multitude of neo-epitopes, underpin both ME/CFS and depression, while greater autoimmune responses directed against anchorage molecules and oxidatively modified neo-epitopes discriminate patients with ME/CFS from those with depression. These autoimmune responses directed against neoantigenic determinants may play a role in the dysregulation of key cellular functions in both disorders, e.g. intracellular signal transduction, cellular differentiation and apoptosis, but their impact may be more important in ME/CFS than in depression.
Myristic acid has been extensively used for fabrication of phase change materials for thermal energy storage applications. The objective of present research was to investigate the influence of biofield treatment on physical and thermal... more
Myristic acid has been extensively used for fabrication of phase change materials for thermal energy storage applications. The objective of present research was to investigate the influence of biofield treatment on physical and thermal properties of myristic acid. The study was performed in two groups (control and treated). The control group remained as untreated, and biofield treatment was given to treated group. The control and treated myristic acid were characterized by X-ray diffraction (XRD), Differential scanning calorimetry (DSC), Thermogravimetric analysis (TGA), Fourier transform infrared (FT-IR) spectroscopy, and Laser particle size analyzer. XRD results revealed alteration in intensity of peaks as well as significant increase in crystallite size (27.07%) of treated myristic acid with respect to control. DSC study showed increase in melting temperature of treated myristic acid as compared to control. Nevertheless, significant change (10.16%) in latent heat of fusion (∆H) was observed in treated myristic acid with respect to control. TGA analysis of treated myristic acid showed less weight loss (31.33%) as compared to control sample (60.49%). This may be due to increase in thermal stability of treated myristic acid in comparison with control. FT-IR results showed increase in frequency of –CH2 and C=O stretching vibrations, probably associated with enhanced bond strength and force constant of the respective bonds. The particle size analyzer showed significant decrease in average particle size (d50 and d99) of treated myristic acid with respect to control. Overall, the results showed significant alteration in physical, spectroscopic and thermal properties of myristic acid. The enhanced crystallite size, and thermal stability of treated myristic acid showed that treated myristic acid could be used as phase change material for thermal energy storage applications.
Myristic acid has been extensively used for fabrication of phase change materials for thermal energy storage applications. The objective of present research was to investigate the influence of biofield treatment on physical and thermal... more
Myristic acid has been extensively used for fabrication of phase change materials for thermal energy storage applications. The objective of present research was to investigate the influence of biofield treatment on physical and thermal properties of myristic acid. The study was performed in two groups (control and treated). The control group remained as untreated, and biofield treatment was given to treated group. The control and treated myristic acid were characterized by X-ray diffraction (XRD), Differential scanning calorimetry (DSC), Thermogravimetric analysis (TGA), Fourier transform infrared (FT-IR) spectroscopy, and Laser particle size analyzer. XRD results revealed alteration in intensity of peaks as well as significant increase in crystallite size (27.07%) of treated myristic acid with respect to control. DSC study showed increase in melting temperature of treated myristic acid as compared to control. Nevertheless, significant change (10.16%) in latent heat of fusion (∆H) was observed in treated myristic acid with respect to control. TGA analysis of treated myristic acid showed less weight loss (31.33%) as compared to control sample (60.49%). This may be due to increase in thermal stability of treated myristic acid in comparison with control. FT-IR results showed increase in frequency of –CH2 and C=O stretching vibrations, probably associated with enhanced bond strength and force constant of the respective bonds. The particle size analyzer showed significant decrease in average particle size (d50 and d99) of treated myristic acid with respect to control. Overall, the results showed significant alteration in physical, spectroscopic and thermal properties of myristic acid. The enhanced crystallite size, and thermal stability of treated myristic acid showed that treated myristic acid could be used as phase change material for thermal energy storage applications. .
The adenosine monophosphate (AMP)-activated protein kinase (AMPK) regulates whole-body and cellular energy balance in response to energy demand and supply. AMPK is an αβγ heterotrimer activated by decreasing concentrations of adenosine... more
The adenosine monophosphate (AMP)-activated protein kinase (AMPK) regulates whole-body and cellular energy balance in response to energy demand and supply. AMPK is an αβγ heterotrimer activated by decreasing concentrations of adenosine triphosphate (ATP) and increasing AMP concentrations. AMPK activation depends on phosphorylation of the α catalytic subunit on threonine-172 (Thr172) by kinases LKB1 or CaMKKβ, and this is promoted by AMP binding to the γ subunit. AMP sustains activity by inhibiting dephosphorylation of α-Thr172, whereas ATP promotes dephosphorylation. Adenosine diphosphate (ADP), like AMP, bound to γ sites 1 and 3 and stimulated α-Thr172 phosphorylation. However, in contrast to AMP, ADP did not directly activate phosphorylated AMPK. In this way, both ADP/ATP and AMP/ATP ratios contribute to AMPK regulation.
A Role for N-Myristoylation in Protein Targeting: ... NADH-Cytochrome b5 Reductase Requires Myristic Acid for ... Association with Outer Mitochondrial But Not ER Membranes ... Nica Borgese,** Diego Aggujaro,* Paola Carrera, ~ Grazia... more
A Role for N-Myristoylation in Protein Targeting: ... NADH-Cytochrome b5 Reductase Requires Myristic Acid for ... Association with Outer Mitochondrial But Not ER Membranes ... Nica Borgese,** Diego Aggujaro,* Paola Carrera, ~ Grazia Pietrini,* and Monique Bassetti* * ...
Background: Inverse associations between dairy intake and the risk of type 2 diabetes have been shown, but more studies are needed, especially from low- and middle-income countries. Objective: The objective was to describe the association... more
Background: Inverse associations between dairy intake and the risk of type 2 diabetes have been shown, but more studies are needed, especially from low- and middle-income countries. Objective: The objective was to describe the association between dairy products and direct measures of glycemic status in adults without known diabetes. Design: The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) includes 15,105 adults, aged 35–74 y, enrolled from universities and research institutions in 6 Brazilian capital cities. We excluded participants with a known diabetes diagnosis, cardiovascular diseases, and cancer. Dairy consumption was assessed by a food-frequency questionnaire, and we computed servings per day for total and subgroups of dairy. Associations with fasting blood glucose (FG) and fasting insulin, 2-h postload glucose (PG), 2-h postload insulin (PI), glycated hemoglobin (Hb A1c), and homeostasis model assessment of insulin resistance (HOMA-IR) were assessed through mult...
BL/VL3 radiation leukemia virus (RadLV) is a thymotropic, highly leukemogenic murine leukemia virus (MuLV) which is unable to replicate in vitro in mouse fibroblasts. We have previously reported that the U3 long terminal repeat region of... more
BL/VL3 radiation leukemia virus (RadLV) is a thymotropic, highly leukemogenic murine leukemia virus (MuLV) which is unable to replicate in vitro in mouse fibroblasts. We have previously reported that the U3 long terminal repeat region of its genome is responsible for this block (E. Rassart, Y. Paquette, and P. Jolicoeur, J. Virol. 62:3840-3848, 1988). By using hybrids of permissive and resistant cells infected with BL/VL3 RadLV or fibrotropic MuLV, we found that the resistant phenotype was dominant. Investigation to determine at which step of the virus cycle the block operates revealed that integration, transcription, and translation of the BL/VL3 viral genome occurred at normal levels in nonpermissive cells. The BL/VL3 RadLV Pr65gag proteins made in nonpermissive cells were also myristylated and located at the membrane, and the levels of their cleaved products were similar to those of fibrotropic MuLV. However, processing of BL/VL3 RadLV Pr85env was impaired in nonpermissive cells....
We have obtained evidence that poliovirus and other picornavirus particles are specifically modified by having myristic acid covalently bound to a capsid protein. The electron density map ofpoliovirus confirms the position of the... more
We have obtained evidence that poliovirus and other picornavirus particles are specifically modified by having myristic acid covalently bound to a capsid protein. The electron density map ofpoliovirus confirms the position of the myristate molecule and defines its location in the virus particle. Analogies with other myristylated proteins suggest that the myristate moiety in picornaviruses may be involved in capsid assembly or in the entry of virus into cells.