Abstract Fatty acid-binding proteins (FABP) are highly abundant cytosolic proteins that are expressed in most mammalian tissues. In the intestinal enterocyte, both liver- (LFABP; FABP1) and ...intestinal FABPs (IFABP; FABP2) are expressed. These proteins display high-affinity binding for long-chain fatty acids (FA) and other hydrophobic ligands; thus, they are believed to be involved with uptake and trafficking of lipids in the intestine. In vitro studies have identified differences in ligand-binding stoichiometry and specificity, and in mechanisms of FA transfer to membranes, and it has been hypothesized that LFABP and IFABP have different functions in the enterocyte. Studies directly comparing LFABP- and IFABP-null mice have revealed markedly different phenotypes, indicating that these proteins indeed have different functions in intestinal lipid metabolism and whole body energy homeostasis. In this review, we discuss the evolving knowledge of the functions of LFABP and IFABP in the intestinal enterocyte.
Tyrosine kinase inhibitors were found to be clinically effective for treatment of patients with certain subsets of cancers carrying somatic mutations in receptor tyrosine kinases. However, the ...duration of clinical response is often limited, and patients ultimately develop drug resistance. Here, we use single-cell RNA sequencing to demonstrate the existence of multiple cancer cell subpopulations within cell lines, xenograft tumors and patient tumors. These subpopulations exhibit epigenetic changes and differential therapeutic sensitivity. Recurrently overrepresented ontologies in genes that are differentially expressed between drug tolerant cell populations and drug sensitive cells include epithelial-to-mesenchymal transition, epithelium development, vesicle mediated transport, drug metabolism and cholesterol homeostasis. We show analysis of identified markers using the LINCS database to predict and functionally validate small molecules that target selected drug tolerant cell populations. In combination with EGFR inhibitors, crizotinib inhibits the emergence of a defined subset of EGFR inhibitor-tolerant clones. In this study, we describe the spectrum of changes associated with drug tolerance and inhibition of specific tolerant cell subpopulations with combination agents.
We study the impact of spin-exchange collisions on the dynamics of Bose-Einstein condensation by rapidly cooling a chromium multicomponent Bose gas. Despite relatively strong spin-dependent ...interactions, the critical temperature for Bose-Einstein condensation is reached before the spin degrees of freedom fully thermalize. The increase in density due to Bose-Einstein condensation then triggers spin dynamics, hampering the formation of condensates in spin-excited states. Small metastable spinor condensates are, nevertheless, produced, and they manifest in strong spin fluctuations.
We calculate the evaporative cooling dynamics of trapped one-dimensional Bose-Einstein condensates for parameters leading to a range of condensates and quasicondensates in the final equilibrium ...state, using the classical fields method. We confirm that solitons are created during the evaporation process by the Kibble-Zurek mechanism, but subsequently dissipate during thermalization. However, their signature remains in the phase coherence length, which is approximately conserved during dissipation in this system.
Abstract
Introduction
Healthcare-associated infections (HAI) and bacterial antimicrobial resistance posed a therapeutic risk during the coronavirus disease 2019 (COVID-19) pandemic. The aim of this ...study was to analyze the HAIs in COVID-19 patients in the Intensive Care Unit (ICU) and non-ICU at the University Hospital in Krakow (UHK) with an emphasis on the susceptibility of the most frequently isolated pathogens and the prevalence of extensively drug resistant (XDR) microorganisms.
Methods
This laboratory-based study was carried out at the University Hospital in Krakow in the ICU and non-ICUs dedicated to COVID-19 patients between May 2021 and January 2022. All isolates of
Klebsiella pneumoniae
were analyzed using PFGE protocol.
Results
292 independent HAI cases were identified, with the predominance of urinary tract infections (UTI), especially in the non-ICU setting. The most common ICU syndrome was pneumonia (PNA). The prevalence of XDR organisms was 22.6% in the ICU and 14.8% in non-ICUs among all isolates. The incidence of carbapenem-resistant Enterobacteriaceae infection was 24.8 cases per 10,000 hospitalizations and the carbapenem-resistant
A. baumannii
infection incidence was 208.8 cases per 10,000 hospitalizations. The prevalence of XDR strains was highest in
Acinetobacter spp
, in PNA cases. The PFGE typing demonstrated that almost all XDR strains varied widely from each other.
Conclusions
In this study, there was a high incidence of HAI in COVID-19 patients, especially when compared to Western Europe and the United States. Similarly, the prevalence of XDR microorganisms, especially XDR-
A.baumannii
, was also high. PFGE did not confirm the horizontal spread of any organism strains.
The enterocyte expresses two fatty acid-binding proteins (FABP), intestinal FABP (IFABP; FABP2) and liver FABP (LFABP; FABP1). LFABP is also expressed in liver. Despite ligand transport and binding ...differences, it has remained uncertain whether these intestinally coexpressed proteins, which both bind long chain fatty acids (FA), are functionally distinct. Here, we directly compared IFABP−/− and LFABP−/− mice fed high fat diets containing long chain saturated or unsaturated fatty acids, reasoning that providing an abundance of dietary lipid would reveal unique functional properties. The results showed that mucosal lipid metabolism was indeed differentially modified, with significant decreases in FA incorporation into triacylglycerol (TG) relative to phospholipid (PL) in IFABP−/− mice, whereas LFABP−/− mice had reduced monoacylglycerol incorporation in TG relative to PL, as well as reduced FA oxidation. Interestingly, striking differences were found in whole body energy homeostasis; LFABP−/− mice fed high fat diets became obese relative to WT, whereas IFABP−/− mice displayed an opposite, lean phenotype. Fuel utilization followed adiposity, with LFABP−/− mice preferentially utilizing lipids, and IFABP−/− mice preferentially metabolizing carbohydrate for energy production. Changes in body weight and fat may arise, in part, from altered food intake; mucosal levels of the endocannabinoids 2-arachidonoylglycerol and arachidonoylethanolamine were elevated in LFABP−/−, perhaps contributing to increased energy intake. This direct comparison provides evidence that LFABP and IFABP have distinct roles in intestinal lipid metabolism; differential intracellular functions in intestine and in liver, for LFABP−/− mice, result in divergent downstream effects at the systemic level.
Background: Intestinal and liver fatty acid-binding proteins (IFABP and LFABP) are coexpressed in the enterocyte, but their individual functions are not known.
Results: High fat feeding promotes different phenotypes in IFABP- and LFABP-null mice.
Conclusion: IFABP and LFABP have unique intracellular functions, which in turn produce divergent whole body effects.
Significance: Enterocyte FABP ablation modulates intestinal lipid metabolism, which contributes to altered systemic energy homeostasis.
In this work we present a very simple and efficient numerical scheme which can be applied to study the dynamics of bosonic systems like, for instance, spinor Bose-Einstein condensates (BEC) with ...non-local interactions but equally well works for Fermi gases. The method we use is a modification of well known Split Operator Method (SOM). We carefully examine this algorithm in the case of F=1 spinor BEC without and with dipolar interactions and for strongly interacting two-component Fermi gas. Our extension of the SOM method has many advantages: it is fast, stable, and keeps constant all the physical constraints (constants of motion) at high level.
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