- Optimization of CFTR gating through the evolution of its extracellular loops. [Journal Article]J Gen Physiol. 2023 Apr 03; 155(4)JG
- CFTR chloride channel mutations cause the lethal and incurable disease cystic fibrosis (CF). CFTR is activated by phosphorylation, and phosphorylated channels exhibit "bursting" behavior-"bursts" of openings separated by short "flickery" closures and flanked by long "interburst" closures-driven by ATP binding/hydrolysis at two nucleotide-binding domains. The human channel (hCFTR) and the distant …
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- Design of transition metal complexes containing a P-E radical motif. [Journal Article]Dalton Trans. 2023 Jan 31 [Online ahead of print]DT
- Recently, we have synthesized phosphane W(CO)5 complexes containing a P-O-TEMP ligand motif as bench-stable precursors of thermally accessible phosphanoxyl complex radicals possessing a ligand with a P-O˙ group. In this work, extensive dispersion-corrected DFT calculations are used to explore both W(CO)5 and Fe(CO)4 phosphane complexes containing the P-E-TEMP ligands (E = O, S, NMe, and PMe) in o…
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- Type 2 Diabetes and HDL dysfunction: a key contributor to Glycemic Control. [Journal Article]Curr Med Chem. 2023 Feb 01 [Online ahead of print]CM
- High-density lipoproteins (HDL) have been shown to exert multiple cardioprotective and antidiabetic functions, such as their ability to promote cellular cholesterol efflux and their antioxidant, anti-inflammatory, and antiapoptotic properties. Type 2 diabetes (T2D) is usually associated with low high-density lipoprotein cholesterol (HDL-C) levels as well as with significant alterations in the HDL…
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- Quantification of Carboxylate-bridged Di-zinc Site Stability in Protein Due Ferri by Single-molecule Force Spectroscopy. [Journal Article]Protein Sci. 2023 Jan 31 [Online ahead of print]PS
- Carboxylate-bridged diiron proteins belong to a protein family involved in different physiological processes. These proteins share the conservative EXXH motif, which provides the carboxylate bridge and is critical for metal binding. Here, we choose de novo-designed due ferri protein DFsc, a four-helical protein with two EXXH motifs as a model protein, to study the stability of the carboxylate-bri…
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- Exploring the Folding Mechanism of Dimeric Superoxide Dismutase. [Journal Article]J Phys Chem B. 2023 Jan 30 [Online ahead of print]JP
- The Cu/Zn Human Superoxide Dismutase (SOD1) is a dimeric metalloenzyme whose genetic mutations are directly related to amyotrophic lateral sclerosis (ALS), so understanding its folding mechanism is of fundamental importance. Currently, the SOD1 dimer formation is studied via molecular dynamics simulations using a simplified structure-based model and an all-atom model. Results from the simplified …
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- Apo- and holo- transferrin differentially interact with ferroportin and hephaestin to regulate iron release at the blood-brain barrier. [Preprint]bioRxiv. 2023 Jan 10B
- CONCLUSIONS: These novel findings provide a molecular mechanism for apo- and holo-Tf regulation of iron release from endothelial cells. They further demonstrate how hepcidin impacts these protein-protein interactions, and offer a model for how holo-Tf and hepcidin corporate to suppress iron release. We have established a more thorough understanding of the mechanisms behind iron release regulation with great clinical impact for a variety of neurological conditions in which iron release is dysregulated.
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- Apo- and holo- transferrin differentially interact with ferroportin and hephaestin to regulate iron release at the blood-brain barrier. [Preprint]Res Sq. 2023 Jan 17RS
- Background : Apo- (iron free) and holo- (iron bound) transferrin (Tf) participate in precise regulation of brain iron uptake at endothelial cells of the blood-brain barrier. Apo-Tf indicates an iron deficient environment and stimulates iron release, while holo-Tf indicates an iron sufficient environment and suppresses additional iron release. Free iron is exported through ferroportin, with hephae…
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- Momelotinib versus danazol in symptomatic patients with anaemia and myelofibrosis (MOMENTUM): results from an international, double-blind, randomised, controlled, phase 3 study. [Randomized Controlled Trial]Lancet. 2023 Jan 28; 401(10373):269-280.Lct
- CONCLUSIONS: Treatment with momelotinib, compared with danazol, resulted in clinically significant improvements in myelofibrosis-associated symptoms, anaemia measures, and spleen response, with favourable safety. These findings support the future use of momelotinib as an effective treatment in patients with myelofibrosis, especially in those with anaemia.
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- Surface LDLR is a major receptor for lipoprotein(a) clearance in male mice lacking PCSK9. [Journal Article]Biochim Biophys Acta Mol Cell Biol Lipids. 2023 Jan 25 [Online ahead of print]BB
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- Australian Atherosclerosis Society Position Statement on Lipoprotein(a): Clinical and Implementation Recommendations. [Journal Article]Heart Lung Circ. 2023 Jan 25 [Online ahead of print]HL
- This position statement provides guidance to cardiologists and related specialists on the management of adult patients with elevated lipoprotein(a) [Lp(a)]. Elevated Lp(a) is an independent and causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve disease (CAVD). While circulating Lp(a) levels are largely determined by ancestry, they are also influenced b…
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- Novel gas exchange analysis in COVID-19 lung disease. [Editorial]
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- Relationship of Apolipoprotein(a) Isoform Size with Clearance and Production of Lipoprotein(a) in a Diverse Cohort. [Journal Article]J Lipid Res. 2023 Jan 24 [Online ahead of print]JL
- Lipoprotein(a) [Lp(a)] has two main proteins, apolipoprotein B100 (apoB100) and apolipoprotein(a) [apo(a)]. High levels of Lp(a) confer an increased risk for atherosclerotic cardiovascular disease (ASCVD). Most people have two circulating isoforms of apo(a) differing in their molecular mass, determined by the number of Kringle IV Type 2 repeats. Previous studies report a strong inverse relationsh…
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- Stepwise assembly of the active site of [NiFe]-hydrogenase. [Journal Article]Nat Chem Biol. 2023 Jan 26 [Online ahead of print]NC
- [NiFe]-hydrogenases are biotechnologically relevant enzymes catalyzing the reversible splitting of H2 into 2e- and 2H+ under ambient conditions. Catalysis takes place at the heterobimetallic NiFe(CN)2(CO) center, whose multistep biosynthesis involves careful handling of two transition metals as well as potentially harmful CO and CN- molecules. Here, we investigated the sequential assembly of the …
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- Impact of Rabeprazole on APO-Dabigatran Exposure in Healthy Volunteers. [Journal Article]CJC Open. 2023 Jan; 5(1):1-7.CO
- CONCLUSIONS: When APO-dabigatran is administered with rabeprazole, the exposure to dabigatran is reduced by about 30%, which is similar to the level observed with Pradaxa when it was co-administered with a proton pump inhibitor. However, the finding that one-third of participants had a > 50% reduction in exposure is concerning, and it highlights the need for caution in patients who have, or are at risk of, reduced gastric acidity.
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- Ixodes ricinus ticks have a functional association with Midichloria mitochondrii. [Journal Article]Front Cell Infect Microbiol. 2022; 12:1081666.FC
- In addition to being vectors of pathogenic bacteria, ticks also harbor intracellular bacteria that associate with ticks over generations, aka symbionts. The biological significance of such bacterial symbiosis has been described in several tick species but its function in Ixodes ricinus is not understood. We have previously shown that I. ricinus ticks are primarily inhabited by a single species of…
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- Probing into the Flap-Dimer Dynamics of the Mycobacterium Tuberculosis Kasa Enzyme Binding Landscape provides The Underlying Inhibitory Mechanisms Of JSF-3285 And 5G. [Journal Article]Curr Top Med Chem. 2023 Jan 25 [Online ahead of print]CT
- CONCLUSIONS: These findings provide a background for a new structure-based design of novel KasA inhibitors.
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- Design of a gold clustering site in an engineered apo-ferritin cage. [Journal Article]
- Water-soluble and biocompatible protein-protected gold nanoclusters (Au NCs) hold great promise for numerous applications. However, design and precise regulation of their structure at an atomic level remain challenging. Herein, we have engineered and constructed a gold clustering site at the 4-fold symmetric axis channel of the apo-ferritin cage. Using a series of X-ray crystal structures, we eva…
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- Intramolecular charge-transfer enhances energy transfer efficiency in carotenoid-reconstituted light-harvesting 1 complex of purple photosynthetic bacteria. [Journal Article]
- In bacterial photosynthesis, the excitation energy transfer (EET) from carotenoids to bacteriochlorophyll a has a significant impact on the overall efficiency of the primary photosynthetic process. This efficiency can be enhanced when the involved carotenoid has intramolecular charge-transfer (ICT) character, as found in light-harvesting systems of marine alga and diatoms. Here, we provide insigh…
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- Structural insights into the elevator-type transport mechanism of a bacterial ZIP metal transporter. [Journal Article]
- The Zrt-/Irt-like protein (ZIP) family consists of ubiquitously expressed divalent metal transporters critically involved in maintaining systemic and cellular homeostasis of zinc, iron, and manganese. Here, we present a study on a prokaryotic ZIP from Bordetella bronchiseptica (BbZIP) by combining structural biology, evolutionary covariance, computational modeling, and a variety of biochemical as…
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- Apolipoprotein Proteomics for Residual Lipid-Related Risk in Coronary Heart Disease. [Journal Article]Circ Res. 2023 Jan 24 [Online ahead of print]CircR
- CONCLUSIONS: Apolipoproteins were associated with CHD independent of conventional risk factors and lipids, suggesting apolipoproteins could help to identify patients with residual lipid-related risk and guide personalized approaches to CHD risk reduction.
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- Lutein nanodisks protect human retinal pigment epithelial cells from UV light-induced damage. [Journal Article]
- The hydrophobic carotenoid, lutein, was conferred with aqueous solubility upon formulation into reconstituted discoidal high density lipoprotein particles, termed lutein nanodisks (ND). When formulated with phosphatidylcholine (PC), apolipoprotein (apo) A-I and lutein (formulation ratio = 5 mg PC/2 mg apoA-I/1 mg lutein), lutein solubilization efficiency in phosphate buffered saline (PBS) was ~90…
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- Effects of peroxisome proliferator activated receptor-α agonist on growth performance, blood profiles, gene expression related to liver fat metabolism in broilers fed diets containing corn naturally contaminated with mycotoxins. [Journal Article]
- This study was conducted to determine the subclinical symptom of broilers exposure to mycotxoins from corn naturally contaminated, and the preventive effect with peroxisome proliferator activated receptor-α (PPARα) agonist (Wy-14643) supplementation. A total of 360 one-day -old male Arbor Acres broilers were randomly distributed into 4 treatments with 9 replicates of 10 birds. Dietary treatments …
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- Identification of Plasma Proteomic Biomarkers in Patients with Mild Cognitive Impairment. [Journal Article]
- Plasma proteomic profiling may provide novel biomarkers for the identification of mild cognitive impairment (MCI). The early diagnosis of MCI still remains a challenging task due to its diverse origin. Currently, molecular approaches have been used to identify MCI diversified origin as its onset is governed by a variety of molecular changes. Therefore, we aimed to find out molecular alteration in…
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- Relationship of idiopathic femoral head necrosis with blood lipid metabolism and coagulation function: A propensity score-based analysis. [Journal Article]
- CONCLUSIONS: IONFH has strong associations with blood lipid metabolism and coagulation function, which provide an avenue for exploring the mechanism of IONFH.
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- Consumption of Eggs Alone or Enriched with Annatto (Bixa orellana L.) Does Not Increase Cardiovascular Risk in Healthy Adults-A Randomized Clinical Trial, the Eggant Study. [Randomized Controlled Trial]
- Most atherosclerotic cardiovascular diseases can be prevented by modifying lifestyles, including unhealthy diets. Eggs contain important carotenoids that may impact cardiovascular risk. The lipid nature of eggs can improve the bioavailability of other carotenoids, such as Annatto (Bixa orellana L.), with reported antioxidant properties. Although numerous studies have shown that there is no associ…
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- Protoporphyrin IX Binds to Iron(II)-Loaded and to Zinc-Loaded Human Frataxin. [Journal Article]
- (1) Background: Human frataxin is an iron binding protein that participates in the biogenesis of iron sulfur clusters and enhances ferrochelatase activity. While frataxin association to other proteins has been extensively characterized up to the structural level, much less is known about the putative capacity of frataxin to interact with functionally related metabolites. In turn, current knowledg…
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- Enhancement of High-Density Lipoprotein (HDL) Quantity and Quality by Regular and Habitual Exercise in Middle-Aged Women with Improvements in Lipid and Apolipoprotein Profiles: Larger Particle Size and Higher Antioxidant Ability of HDL. [Journal Article]
- Regular exercise, especially aerobic exercise, is beneficial for increasing serum high-density lipoprotein-cholesterol (HDL-C) levels in the general population. In addition to the HDL-C quantity, exercise enhances HDL functionality, antioxidants, and cholesterol efflux. On the other hand, the optimal intensity and frequency of exercise to increase HDL quantity and enhance HDL quality in middle-ag…
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- Structural Insights Uncover the Specific Phosphoinositide Recognition by the PH1 Domain of Arap3. [Journal Article]
- Arap3, a dual GTPase-activating protein (GAP) for the small GTPases Arf6 and RhoA, plays key roles in regulating a wide range of biological processes, including cancer cell invasion and metastasis. It is known that Arap3 is a PI3K effector that can bind directly to PI(3,4,5)P3, and the PI(3,4,5)P3-mediated plasma membrane recruitment is crucial for its function. However, the molecular mechanism o…
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- Biomarkers for Premature Coronary Artery Disease (PCAD): A Case Control Study. [Journal Article]
- Coronary artery disease (CAD) is often associated with the older generation. However, in recent years, there is an increasing trend in the prevalence of CAD among the younger population; this is known as premature CAD. Although biomarkers for CAD have been established, there are limited studies focusing on premature CAD especially among the Malay male population. Thus, the aim of this research wa…
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