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Motivators, barriers and strategies of weight management: A cross-sectional study among Finnish adults.
2018
Abstract Background Weight management (WM) is an ongoing global challenge. The purpose of this study was to analyze motivators, barriers, and strategies of WM among Finnish adults. Methods Data were collected in the ‘KULUMA’ (Consumers at the Weight Management Market) project among 667 community-dwelling adults in Eastern and Central Finland (Kuopio and Jyvaskyla). The self-reported questionnaire collected background information and responses to motivators, barriers, and strategy items. Principal component analysis (PCA) was used to extract components of motivators, barriers, and strategies of WM, along with K-means clustering to categorize the participants. Results About 55% of the respond…
Analysis of substrate binding in individual active sites of bifunctional human ATIC
2018
Aminoimidazolecarboxamide ribonucleotide formyl transferase (AICARFT): Inosine monophosphate cyclohydrolase (IMPCH, collectively called ATIC) is a bifunctional enzyme that catalyses the penultimate and final steps in the purine de novo biosynthesis pathway. The bifunctional protein is dimeric and each monomer contains two different active sites both of which are capable of binding nucleotide substrates, this means to a potential total of four distinct binding events might be observed. Within this work we used a combination of site-directed and truncation mutants of ATIC to independently investigate the binding at these two sites using calorimetry. A single S10W mutation is sufficient to blo…
Feedback Regulation of Syk by Protein Kinase C in Human Platelets
2019
The spleen tyrosine kinase (Syk) is essential for immunoreceptor tyrosine-based activation motif (ITAM)-dependent platelet activation, and it is stimulated by Src-family kinase (SFK)-/Syk-mediated phosphorylation of Y352 (interdomain-B) and Y525/526 (kinase domain). Additional sites for Syk phosphorylation and protein interactions are known but remain elusive. Since Syk S297 phosphorylation (interdomain-B) was detected in platelets, we hypothesized that this phosphorylation site regulates Syk activity via protein kinase C (PKC)-and cyclic adenosine monophosphate (cAMP)-dependent pathways. ADP, the GPVI-agonist convulxin, and the GPIb&alpha
Relevance of assessing the uterine microbiota in infertility
2018
Technical advances in massive parallel sequencing have allowed the characterization of the whole reproductive tract microbiome in all the compartments beyond the vagina. The microbiota in the uterine cavity seem to be a continuum from the microbiota in the vagina, but several works have reported significant differences between vaginal and endometrial microbiota, highlighting the relevance of assessing the upper genital tract microbiota to better understand the potential roles of bacteria in the physiological and pathological processes taking place in the uterine cavity, including embryo implantation, pregnancy maintenance, and other gynecological diseases. However, the study of the endometr…
In Silico Insights towards the Identification of NLRP3 Druggable Hot Spots
2019
NLRP3 (NOD-like receptor family, pyrin domain-containing protein 3) activation has been linked to several chronic pathologies, including atherosclerosis, type-II diabetes, fibrosis, rheumatoid arthritis, and Alzheimer’s disease. Therefore, NLRP3 represents an appealing target for the development of innovative therapeutic approaches. A few companies are currently working on the discovery of selective modulators of NLRP3 inflammasome. Unfortunately, limited structural data are available for this target. To date, MCC950 represents one of the most promising noncovalent NLRP3 inhibitors. Recently, a possible region for the binding of MCC950 to the NLRP3 protein was described but no details were …
Phytochemical inhibitors of the NLRP3 inflammasome for the treatment of inflammatory diseases
2021
The NLRP3 inflammasome holds a crucial role in innate immune responses. Pathogen- and danger-associated molecular patterns may initiate inflammasome activation and following inflammatory cytokine release. The inflammasome formation and its-associated activity are involved in various pathological conditions such as cardiovascular, central nervous system, metabolic, renal, inflammatory and autoimmune diseases. Although the mechanism behind NLRP3-mediated disorders have not been entirely illuminated, many phytochemicals and medicinal plants have been described to prevent inflammatory disorders. In the present review, we mainly introduced phytochemicals inhibiting NLRP3 inflammasome in addition…
Cooperation of Secondary Transporters and Sensor Kinases in Transmembrane Signalling
2016
Many membrane-bound sensor kinases require accessory proteins for function. The review describes functional control of membrane-bound sensors by transporters. The C4-dicarboxylate sensor kinase DcuS requires the aerobic or anaerobic C4-dicarboxylate transporters DctA or DcuB, respectively, for function and forms DctA/DcuS or DcuB/DcuS sensor complexes. Free DcuS is in the permanent (ligand independent) ON state. The DctA/DcuS and DcuB/DcuS complexes, on the other hand, control expression in response to C4-dicarboxylates. In DctA/DcuS, helix 8b of DctA and the PASC domain of DcuS are involved in interaction. The stimulus is perceived by the extracytoplasmic sensor domain (PASP) of DcuS. The …
Double-exponential kinetics of binding and redistribution of the fluorescent dyes in cell membranes witness for the existence of lipid microdomains.
2018
Abstract New technique of detecting lateral heterogeneity of the plasma membrane of living cells by means of membrane-binding fluorescent dyes is proposed. The kinetics of dye incorporation into the membrane or its lateral diffusion inside the membrane is measured and decomposed into exponential components by means of the Maximum Entropy Method. Two distinct exponential components are obtained consistently in all cases for several fluorescent dyes, two different cell lines and in different types of experiments including spectroscopy, flow cytometry and fluorescence recovery after photobleaching. These components are attributed to the liquid-ordered and disordered phases in the plasma membra…
A selective inhibitor of the Polo-box domain of Polo-like kinase 1 identified by virtual screening
2018
Graphical abstract
Allosteric Cross-Talk among Spike’s Receptor-Binding Domain Mutations of the SARS-CoV-2 South African Variant Triggers an Effective Hijacking of Huma…
2021
The rapid and relentless emergence of novel highly transmissible SARS-CoV-2 variants, possibly decreasing vaccine efficacy, currently represents a formidable medical and societal challenge. These variants frequently hold mutations on the Spike protein's receptor-binding domain (RBD), which, binding to the angiotensin-converting enzyme 2 (ACE2) receptor, mediates viral entry into host cells. Here, all-atom molecular dynamics simulations and dynamical network theory of the wild-type and mutant RBD/ACE2 adducts disclose that while the N501Y mutation (UK variant) enhances the Spike's binding affinity toward ACE2, the concomitant N501Y, E484K, and K417N mutations (South African variant) aptly ad…