- Polymorphism in disease-related apolipoprotein C-II amyloid fibrils: A structural model for rod-like fibrils. [Journal Article]
- FJFEBS J 2018 May 23
- Human apolipoprotein (apo) C-II is one of several plasma apolipoproteins that form amyloid deposits in vivo and is an independent risk factor for cardiovascular disease. Lipid-free apoC-II readily se...
Human apolipoprotein (apo) C-II is one of several plasma apolipoproteins that form amyloid deposits in vivo and is an independent risk factor for cardiovascular disease. Lipid-free apoC-II readily self-assembles into twisted-ribbon amyloid fibrils but forms straight, rod-like amyloid fibrils in the presence of low concentrations of micellar phospholipids. Charge mutations exerted significantly different effects on rod-like fibril formation compared to their effects on twisted-ribbon fibril formation. For instance, the double mutant K30D, D69K apoC-II readily formed twisted-ribbon fibrils, while the rate of rod-like fibril formation in the presence of micellar phospholipid was negligible. Structural analysis of rod-like apoC-II fibrils using hydrogen/deuterium exchange and NMR analysis showed exchange protection consistent with a core cross-β structure comprising the C-terminal 58-76 region. Molecular dynamic simulations of fibril arrangements for this region favored a parallel cross-β structure. X-ray fibre diffraction data for aligned rod-like fibrils showed a major meridional spacing at 4.6 Å and equatorial spacings at 9.7 Å, 23.8 Å and 46.6 Å. The latter two equatorial spacings are not observed for aligned twisted-ribbon fibrils and are predicted for a model involving two cross-β fibrils in an off-set antiparallel structure with 4 apoC-II units per rise of the β-sheet. This model is consistent with the mutational effects on rod-like apoC-II fibril formation. The lipid-dependent polymorphisms exhibited by apoC-II fibrils could determine the properties of apoC-II in renal amyloid deposits and their potential role in the development of cardiovascular disease. This article is protected by copyright. All rights reserved.
- Is Lipid Accumulation Product Associated with an Atherogenic Lipoprotein Profile in Brazilian Subjects? [Journal Article]
- ABArq Bras Cardiol 2018; 110(4):339-347
- CONCLUSIONS: LAP was robustly associated with atherogenic profile of lipoprotein subfractions, independently of multiple confounders.
- 4-Oxo-β-apo-13-carotenone from the cyanobacterium Anabaena cylindrica PCC 7122. [Journal Article]
- CBChem Biodivers 2018 May 22
- Apocarotenoids are widely distributed among living organisms (bacteria, fungi, algae, plants and even animals) and have been associated with several signaling functions. These compounds are generated...
Apocarotenoids are widely distributed among living organisms (bacteria, fungi, algae, plants and even animals) and have been associated with several signaling functions. These compounds are generated by the activity of carotenoid cleavage dioxygenases (CCDs), whose diversity greatly contributes to the large number of apocarotenoids that have been described so far. It is nevertheless expected that a considerable diversity of these molecules is yet to be discovered. In this work, we describe the isolation and structural elucidation of the apocarotenoid 4-oxo-β-apo-13-carotenone from the cultured freshwater cyanobacterium Anabaena cylindrica PCC 7122, corresponding to the first report of this compound from natural sources. This article is protected by copyright. All rights reserved.
- Apolipoprotein E and Atherosclerosis: From Lipoprotein Metabolism to MicroRNA Control of Inflammation. [Review]
- JCJ Cardiovasc Dev Dis 2018 May 23; 5(2)
- Apolipoprotein (apo) E stands out among plasma apolipoproteins through its unprecedented ability to protect against atherosclerosis. Although best recognized for its ability to mediate plasma lipopro...
Apolipoprotein (apo) E stands out among plasma apolipoproteins through its unprecedented ability to protect against atherosclerosis. Although best recognized for its ability to mediate plasma lipoprotein clearance in the liver and protect against macrophage foam cell formation, our recent understanding of the influence that apoE can exert to control atherosclerosis has significantly widened. Among apoE's newfound athero-protective properties include an ability to control exaggerated hematopoiesis, blood monocyte activation and aortic stiffening in mice with hyperlipidemia. Mechanisms responsible for these exciting new properties extend beyond apoE's ability to prevent cellular lipid excess. Rather, new findings have revealed a role for apoE in regulating microRNA-controlled cellular signaling in cells of the immune system and vascular wall. Remarkably, infusions of apoE-responsive microRNA mimics were shown to substitute for apoE in protecting against systemic and vascular inflammation to suppress atherosclerosis in mice with hyperlipidemia. Finally, more recent evidence suggests that apoE may control the release of microvesicles that could modulate cellular signaling, inflammation and atherosclerosis at a distance. These exciting new findings position apoE within the emerging field of intercellular communication that could introduce new approaches to control atherosclerosis cardiovascular disease.
- Treatment of Mal de Debarquement Syndrome in a Deployed Environment. [Journal Article]
- MMMil Med 2018 May 18
- We report the case of a 26-year-old Caucasian female with persistent sensations of forward and reverse movement with spontaneous onset. This worsened over 4 wk. The patient reported an episode of the...
We report the case of a 26-year-old Caucasian female with persistent sensations of forward and reverse movement with spontaneous onset. This worsened over 4 wk. The patient reported an episode of these symptoms 5 mo prior, which lasted for 3 mo before improving. Our case details the treatment of Mal de Debarquement syndrome, or Disembarkment Syndrome, in a deployed military environment. Mal de Debarquement was a term originally coined to describe the persistent sensation of rocking back and forth after disembarking a boat and returning to land. This is normal, and usually only lasts for minutes to hours. When it persists, it is called Mal de Debarquement Syndrome. The onset frequently coincides with travel and most commonly by boat, however it can also occur spontaneously as in this case. Currently, there are three different treatment options. The first involves medications that are often sedating. The second uses magnetic resonance imaging at high frequency to stimulate the areas of the brain thought to be involved. The third option is a form of physical therapy termed re-adaptation of the vestibular ocular reflex. As we were in a deployed military environment the first two options were unsafe and unavailable respectively. We employed an improvised version of re-adaptation of the vestibular ocular reflex. The patient demonstrated a 50% reduction in symptoms following 1 wk of treatment and as a result was safely able to complete her deployment.
- Acute pancreatitis secondary to oral contraceptive-induced hypertriglyceridemia: a case report. [Journal Article]
- GEGynecol Endocrinol 2018 May 21; :1-3
- Hypertriglyceridemia is the third most common cause of acute pancreatitis. Among the causes that lead to secondary hypertriglyceridemia, the use of contraceptive agents is the main reason to be asses...
Hypertriglyceridemia is the third most common cause of acute pancreatitis. Among the causes that lead to secondary hypertriglyceridemia, the use of contraceptive agents is the main reason to be assessed in young women. We report a case of a 31-year-old woman who had suffered two acute pancreatitis episodes secondary to hypertriglyceridemia. In the investigation, the previous medical team indicated a genetic screening before ruling out all secondary causes. LPL, apo CII and apo AV genes were negative for mutations. In the first appointment with us, the patient reported the use of a contraceptive agent for about 2 years. She was instructed to discontinue the drug. After one year of follow-up, her serum triglycerides are within the normal range and a copper intrauterine device was the method chosen by the patient for contraception.
- Activities of purine converting enzymes in heart, liver and kidney mice LDLR-/- and Apo E-/. [Journal Article]
- NNNucleosides Nucleotides Nucleic Acids 2018 May 21; :1-8
- Nucleotide metabolism plays a major role in a number of vital cellular processes such as energetics. This, in turn, is important in pathologies such as atherosclerosis. Three month old atheroscleroti...
Nucleotide metabolism plays a major role in a number of vital cellular processes such as energetics. This, in turn, is important in pathologies such as atherosclerosis. Three month old atherosclerotic mice with knock outs for LDLR and apolipoprotein E (ApoE) were used for the experiments. Activities of AMP-deaminase (AMPD), ecto5'-nucleotidase (e5NT), adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP) were measured in heart, liver and kidney cortex and medulla by analysing conversion of substrates into products using HPLC. The activity of ecto5'-nucleotidase differ in hearts of LDLR-/- and ApoE-/- mice with no differences in ADA and AMPD activity. We noticed highest activity of e5NT in kidney medulla of the models. This model of atherosclerosis characterize with an inhibition of enzyme responsible for production of protective adenosine in heart but not in other organs and different metabolism of nucleotides in kidney medulla.
- The trends and risk factors to predict adverse outcomes in gestational diabetes mellitus: a 10-year experience from 2006 to 2015 in a single tertiary center. [Journal Article]
- OGObstet Gynecol Sci 2018; 61(3):309-318
- CONCLUSIONS: Our study demonstrated the trends and relevant factors associated with the adverse outcomes.
- Combining theoretical and experimental data to decipher CFTR 3D structures and functions. [Journal Article]
- CMCell Mol Life Sci 2018 May 19
- Cryo-electron microscopy (cryo-EM) has recently provided invaluable experimental data about the full-length cystic fibrosis transmembrane conductance regulator (CFTR) 3D structure. However, this expe...
Cryo-electron microscopy (cryo-EM) has recently provided invaluable experimental data about the full-length cystic fibrosis transmembrane conductance regulator (CFTR) 3D structure. However, this experimental information deals with inactive states of the channel, either in an apo, quiescent conformation, in which nucleotide-binding domains (NBDs) are widely separated or in an ATP-bound, yet closed conformation. Here, we show that 3D structure models of the open and closed forms of the channel, now further supported by metadynamics simulations and by comparison with the cryo-EM data, could be used to gain some insights into critical features of the conformational transition toward active CFTR forms. These critical elements lie within membrane-spanning domains but also within NBD1 and the N-terminal extension, in which conformational plasticity is predicted to occur to help the interaction with filamin, one of the CFTR cellular partners.
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- Comparison of two groups for the apolipoprotein E polymorphisms by using next generation sequencing: The first group with three consecutive abortions and the second group with at most one abortion in three consecutive pregnancies. [Journal Article]
- GENEGene 2018 May 17
- The importance of apolipoprotein E genotypes and allelic polymorphisms in the etiology of recurrent miscarriage is controversial. We plan to investigate this in a two-group study involving more than ...
The importance of apolipoprotein E genotypes and allelic polymorphisms in the etiology of recurrent miscarriage is controversial. We plan to investigate this in a two-group study involving more than a thousand participants. In total, 1046 subjects (802 participants in the first group, 244 participants in the second group) were investigated. Women in the first group had a history of ≥3 consecutive spontaneous miscarriage and women in the second group had at most one miscarriage in three consecutive pregnancies. The participants with the following evidence and symptoms were excluded from both groups; structural uterine abnormality, chrosomal abnormalities and polymorphisms, hormonal imbalance, anti-nuclear antibodies, anti-phospholipid antibodies, lupus anticoagulant and homozygous genotype for FV-Leiden, MTHFR C677T, MTHFR A1298C, prothrombin 20210G>A and plasminogen activator inhibitor 4G/5G polymorphisms. We found similar apolipoprotein E allelic frequencies and genotype distributions in both groups. The frequencies of ε2 alleles were 4.1% in the first group and 2.9% in the second group, whereas those of ε3 alleles were 90.8% and 93% in the first group and the second group, respectively and ε4 alleles were 5.1% in the first group and 4.1% in the second group. The genotypes of Apo E observed in the first and the second group respectively were as follows; ε2/ε3 (7.5% and 5.7%), ε3/ε3 (82.7% and 86.5%), ε3/ε4 (8.7% and 7.4%), ε4/ε4 (0.5% and 0.4%) and ε2/ε4 (0.6% and 0). Our data did not support a possible association between apolipoprotein E genotypes and allelic frequencies, and recurrent miscarriages. We believe that the studies excluding the etiological factors that were previously found to be related with any condition are more valuable in the scope of showing the cause-effect relationship.