Altered Membrane Composition Research Articles

Effect of sonication time on physical and foaming properties of pasteurized milk

This study investigates the impact of ultrasonication duration on the properties of milk foam. Milk samples were subjected to ultrasonication for varying durations (1, 3, 5, 7, and 10 min), resulting in different sizes of native fat globules (249.5, 221.5, 222.6, 207.5, and 244.8 nm, respectively). The results indicate that viscosity increases as fat globule size decreases, with slight effect on zeta potential. NanoFoamer was identified as the optimal method providing the highest between foamability and stability (p < 0.05). Notably, foaming performance decreases after 7 min of sonication, highlighting the importance of selecting an appropriate frothing method to achieve the desired foam characteristics. Comparisons with non-ultrasonicated milk suggest that ultrasonication duration not only influences foamability by reducing fat globule size but also enhances foam stability through alterations in the fat globule sizes. Analysis of the foam structure revealed that smaller fat globules initially produce smaller, more numerous air bubbles with polyhedral shapes and well-defined lamellae. However, excessive reduction in fat globule size destabilizes the foam due to competitive protein adsorption and altered membrane composition, resulting in larger, less stable bubbles over time. Exploring ultrasonication times to enhances quality of milk and foam properties, offering significant benefits for dairy processing, product innovation and customer satisfaction.

Impact of ERG6 Gene Deletion on Membrane Composition and Properties in the Pathogenic Yeast Candida glabrata.

The ERG6 gene is crucial for the biosynthesis of ergosterol, a key component of yeast cell membranes. Our study examines the impact of ERG6 gene deletion on the membrane composition and physicochemical properties of the pathogenic yeast Candida glabrata. Specifically, we investigated changes in selected sterol content, phospholipid composition, transmembrane potential, and PDR16 gene activity. Sterol levels were measured using high-performance liquid chromatography, the phospholipid profile was analysed via thin-layer chromatography, transmembrane potential was assessed with fluorescence spectroscopy, and gene expression levels were determined by quantitative PCR. Our findings revealed a depletion of ergosterol, increased zymosterol and eburicol content, an increased phosphatidylcholine and a reduced phosphatidylethanolamine content in the Δerg6 strain compared to the wt. Additionally, the Δerg6 strain exhibited membrane hyperpolarization without changes in PDR16 expression. Furthermore, the Δerg6 strain showed increased sensitivity to the antifungals myriocin and aureobasidine A. These results suggest that ERG6 gene deletion leads to significant alterations in membrane composition and may activates an alternative ergosterol synthesis pathway in the C. glabrata Δerg6 deletion mutant.

Enhancing freeze-thaw tolerance in baker's yeast: strategies and perspectives.

Frozen dough technology is important in modern bakery operations, facilitating the transportation of dough at low temperatures to downstream sales points. However, the freeze-thaw process imposes significant stress on baker's yeast, resulting in diminished viability and fermentation capacity. Understanding the mechanisms underlying freeze-thaw stress is essential for mitigating its adverse effects on yeast performance. This review delves into the intricate mechanisms underlying freeze-thaw stress, focusing specifically on Saccharomyces cerevisiae, the primary yeast used in baking, and presents a wide range of biotechnological approaches to enhance freeze-thaw resistance in S. cerevisiae. Strategies include manipulating intracellular metabolites, altering membrane composition, managing antioxidant defenses, mediating aquaporin expression, and employing adaptive evolutionary and breeding techniques. Addressing challenges and strategies associated with freeze-thaw stress, this review provides valuable insights for future research endeavors, aiming to enhance the freeze-thaw tolerance of baker's yeast and contribute to the advancement of bakery science.

Longitudinal characterization of the metabolome of dairy cows transitioning from one lactation to the next: Investigations in the liver

This study aimed to investigate the metabolic changes in the livers of dairy cows from 1 wk before dry-off to 1 wk after calving. Twelve high-yielding Holstein cows were included in a longitudinal study and housed in a tie-stall barn. The cows were dried off at 6 wk before the expected calving date (dry period length = 42 d). During the entire lactation, the cows were milked twice daily at 0600 and 1700 h. Liver biopsies were taken from each cow at 4 different times: wk -7 (before drying off), -5 (after drying off), -1 and +1 relative to calving. A targeted metabolomics approach was performed by liquid chromatography and flow injection with electrospray ionization triple quadrupole mass spectrometry using the MxP® Quant 500 kit. A total of 185 metabolites in the liver were used for the final data analysis. Principal component analysis (PCA) revealed a clear separation by days of sampling, indicating a notable shift in metabolic phenotype from late lactation to dry period and further changes after calving. Changes were observed in several classes of compounds, including amino acids and biogenic amines. In particular, the changes in acylcarnitines (AcylCN), phosphatidylcholines (PC), sphingomyelins (SM) and bile acids (BA) indicated extensive remodeling of the hepatic lipidome. The changes in AcylCN concentrations in early lactation suggest incomplete fatty acid oxidation in the liver, possibly indicating mitochondrial dysfunction or enzymatic imbalance. In addition, the changes in PC and SM species in early lactation indicate altered cell membrane composition, which may affect cell signaling and functionality. In addition, changes in BA concentrations and profiles indicate dynamic adaptations in BA synthesis, lipid digestion and absorption during the observation period. In particular, PCA analysis showed an overlapping distribution of liver metabolites in primiparous and multiparous cows, indicating no significant difference between these groups. In addition, Volcano plots showed similar liver metabolism between primiparous and multiparous cows, with no significant fold changes (>1.5) in any metabolite at significant P-values (false discovery rate <0.05). These results provide valuable insight into the physiological ranges of liver metabolites during dry period and calving in healthy dairy cows and should contribute to the design and interpretation of future metabolite-based studies of the transition dairy cow.

Alteration of cholesterol content and oxygen level in intestinal organoids after infection with Staphylococcus aureus.

The pathogenicity elicited by Staphylococcus (S.) aureus, one of the best-studied bacteria, in the intestine is not well understood. Recently, we demonstrated that S. aureus infection induces alterations in membrane composition that are associated with concomitant impairment of intestinal function. Here, we used two organoid models, induced pluripotent stem cell (iPSC)-derived intestinal organoids and colonic intestinal stem cell-derived intestinal organoids (colonoids), to examine how sterol metabolism and oxygen levels change in response to S. aureus infection. HPLC quantification showed differences in lipid homeostasis between infected and uninfected cells, characterized by a remarkable decrease in total cellular cholesterol. As the altered sterol metabolism is often due to oxidative stress response, we next examined intracellular and extracellular oxygen levels. Three different approaches to oxygen measurement were applied: (1) cell-penetrating nanoparticles to quantify intracellular oxygen content, (2) sensor plates to quantify extracellular oxygen content in the medium, and (3) a sensor foil system for oxygen distribution in organoid cultures. The data revealed significant intracellular and extracellular oxygen drop after infection in both intestinal organoid models as well as in Caco-2 cells, which even 48 h after elimination of extracellular bacteria, did not return to preinfection oxygen levels. In summary, we show alterations in sterol metabolism and intra- and extracellular hypoxia as a result of S. aureus infection. These results will help understand the cellular stress responses during sustained bacterial infections in the intestinal epithelium.

Adaptation mechanisms of Listeria monocytogenes to quaternary ammonium compounds.

Listeria monocytogenes is ubiquitously found in nature and can easily enter food-processing facilities due to contaminations of raw materials. Several countermeasures are used to combat contamination of food products, for instance, the use of disinfectants that contain quaternary ammonium compounds, such as benzalkonium chloride (BAC) and cetyltrimethylammonium bromide (CTAB). In this study, we assessed the potential of the commonly used wild-type strain EGD-e to adapt to BAC and CTAB under laboratory growth conditions. All BAC-tolerant suppressors exclusively carried mutations in fepR, encoding a TetR-like transcriptional regulator, or its promoter region, likely resulting in the overproduction of the efflux pump FepA. In contrast, CTAB tolerance was associated with mutations in sugR, which regulates the expression of the efflux pumps SugE1 and SugE2. L. monocytogenes strains lacking either FepA or SugE1/2 could still acquire tolerance toward BAC and CTAB. Genomic analysis revealed that the overproduction of the remaining efflux system could compensate for the deleted one, and even in the absence of both efflux systems, tolerant strains could be isolated, which all carried mutations in the diacylglycerol kinase-encoding gene lmo1753 (dgkB). DgkB converts diacylglycerol to phosphatidic acid, which is subsequently reused for the synthesis of phospholipids, suggesting that alterations in membrane composition could be the third adaptation mechanism. IMPORTANCE Survival and proliferation of Listeria monocytogenes in the food industry are ongoing concerns, and while there are various countermeasures to combat contamination of food products, the pathogen still successfully manages to withstand the harsh conditions present in food-processing facilities, resulting in reoccurring outbreaks, subsequent infection, and disease. To counteract the spread of L. monocytogenes, it is crucial to understand and elucidate the underlying mechanism that permits their successful evasion. We present various adaptation mechanisms of L. monocytogenes to withstand two important quaternary ammonium compounds.

Investigating membrane-binding properties of lipoxygenases using surface plasmon resonance

Lipoxygenases (LOXs) catalyze the oxidation of polyunsaturated fatty acids and synthesize oxylipin products that drive important cellular signaling processes in plants and animals. While there has been indirect evidence presented for the interaction of mammalian LOXs with membranes, a quantitative study of the molecular details of LOX-membrane interactions is lacking. Here, we mimicked biological membranes using surface plasmon resonance (SPR) sensor chips derivatized with 2-D planar lipophilic anchors (2D LP) to capture liposomes of varying phospholipid compositions that self-assemble into lipid bilayers on the SPR chip. The sensor chip surfaces were then used to investigate the membrane-binding properties of model LOX enzymes. SPR binding assays displayed reproducible and stable liposome capture to the sensor chip surface that allowed for the detailed characterization of LOX-membrane interactions. Our studies demonstrate a calcium-dependence for the membrane binding activities of coral 8R-LOX and human 15-LOX-2. Furthermore, our data confirm the importance of key membrane insertion loop residues in each of these LOX enzymes for membrane binding activity. Experiments utilizing model plant and human LOXs reveal differences in membrane-binding specificities. Our study establishes and validates a robust SPR-based platform using 2D LP sensor chips that allows for the detailed study of LOX-membrane interactions under different experimental conditions, including altered membrane compositions. Collectively, this investigation improves our overall understanding of LOX-membrane interaction properties, and our SPR-based approach holds potential for future use in the development of LOX-based therapeutics.

The endothelium in lung fibrosis: a core signaling hub in disease pathogenesis?

Pulmonary fibrosis is a progressive chronic lung disease characterized by excessive deposition of extracellular matrix and structural destruction, associated with a severe five year mortality rate. The onset of the disease is thought to be triggered by chronic damage to the alveolar epithelium. Since the pulmonary endothelium is an important component of the alveolar-capillary niche, it is also affected by the initial injury. In addition to ensuring proper gas exchange, the endothelium has critical functional properties, including regulation of vascular tone, inflammatory responses, coagulation and maintenance of vascular homeostasis and integrity. Recent single-cell analyses have shown that shifts in endothelial cell subtypes occur in pulmonary fibrosis. Furthermore, the increased vascular remodeling associated with pulmonary fibrosis leads to deteriorated outcomes for patients, underscoring the importance of the vascular bed in pulmonary fibrosis. To date, the causes and consequences of endothelial and vascular involvement in pulmonary fibrosis are poorly understood. Therefore, it is of great importance to investigate the involvement of endothelial cells and the vascular system in the pathogenesis of the disease. In this review, we will outline the current knowledge on the role of the pulmonary vasculature in pulmonary fibrosis, in terms of abnormal cellular interactions, hyperinflammation, vascular barrier disorders and an altered basement membrane composition. Finally, we will summarize recent advances in extensive therapeutic research and discuss the significant value of novel therapies targeting the endothelium.

The anti-tumor drug 2-hydroxyoleic acid regulates the oncogenic potassium channel Kv10.1

Background2-hydroxyoleic acid (2OHOA) is a synthetic fatty acid with antitumor properties that alters membrane composition and structure, which in turn influences the functioning of membrane proteins and cell signaling. In this study, we propose a novel antitumoral mechanism of 2OHOA accomplished through the regulation of Kv10.1 channels. We evaluated the effects of 2OHOA on Kv10.1 channels expressed in HEK-293 cells by using electrophysiological techniques and a cell proliferation assay.Results2OHOA increased Kv10.1 channel currents in a voltage-dependent manner, shifted its conductance-voltage relationship towards negative potentials, and accelerated its activation kinetics. Moreover, 2OHOA reduced proliferation of cells that exogenously (HEK-293) and endogenously (MCF-7) expressed Kv10.1 channels. It is worth noting that the antiproliferative effect of 2OHOA was maintained in HEK-293 cells expressing a non-conducting mutant of Kv10.1 channel (Kv10.1-F456A), while it did not affect HEK-293 cells not expressing Kv10.1 channels, suggesting that 2OHOA interferes with a non-conducting function of Kv10.1 channels involved in cell proliferation. Finally, we found that 2OHOA can act synergistically with astemizole, a Kv10.1 channel blocker, to decrease cell proliferation more efficiently.ConclusionOur data suggest that 2OHOA decreases cell proliferation, at least in part, by regulating Kv10.1 channels.

Antimicrobial Peptides Can Generate Tolerance by Lag and Interfere with Antimicrobial Therapy.

Antimicrobial peptides (AMPs) are widely distributed molecules secreted mostly by cells of the innate immune system to prevent bacterial proliferation at the site of infection. As with classic antibiotics, continued treatment with AMPs can create resistance in bacteria. However, whether AMPs can generate tolerance as an intermediate stage towards resistance is not known. Here, we show that the treatment of Escherichia coli with different AMPs induces tolerance by lag, particularly for those peptides that have internal targets. This tolerance can be detected as different morphological and physiological changes, which depend on the type of peptide molecule the bacterium has been exposed to. In addition, we show that AMP tolerance can also affect antibiotic treatment. The genomic sequencing of AMP-tolerant strains shows that different mutations alter membrane composition, DNA replication, and translation. Some of these mutations have also been observed in antibiotic-resistant strains, suggesting that AMP tolerance could be a relevant step in the development of antibiotic resistance. Monitoring AMP tolerance is relevant vis-á-vis the eventual therapeutic use of AMPs and because cross-tolerance might favor the emergence of resistance against conventional antibiotic treatments.

Plasma membrane and brain dysfunction of the old: Do we age from our membranes?

One of the characteristics of aging is a gradual hypo-responsiveness of cells to extrinsic stimuli, mainly evident in the pathways that are under hormone control, both in the brain and in peripheral tissues. Age-related resistance, i.e., reduced response of receptors to their ligands, has been shown to Insulin and also to leptin, thyroid hormones and glucocorticoids. In addition, lower activity has been reported in aging for ß-adrenergic receptors, adenosine A2B receptor, and several other G-protein-coupled receptors. One of the mechanisms proposed to explain the loss of sensitivity to hormones and neurotransmitters with age is the loss of receptors, which has been observed in several tissues. Another mechanism that is finding more and more experimental support is related to the changes that occur with age in the lipid composition of the neuronal plasma membrane, which are responsible for changes in the receptors’ coupling efficiency to ligands, signal attenuation and pathway desensitization. In fact, recent works have shown that altered membrane composition—as occurs during neuronal aging—underlies reduced response to glutamate, to the neurotrophin BDNF, and to insulin, all these leading to cognition decay and epigenetic alterations in the old. In this review we present evidence that altered functions of membrane receptors due to altered plasma membrane properties may be a triggering factor in physiological decline, decreased brain function, and increased vulnerability to neuropathology in aging.

Cytostatic effects of structurally different ginsenosides on yeast cells with altered sterol biosynthesis and transport

Triterpene glycosides are a diverse group of plant secondary metabolites, consisting of a sterol-like aglycon and one or several sugar groups. A number of triterpene glycosides show membranolytic activity, and, therefore, are considered to be promising antimicrobial drugs. However, the interrelation between their structure, biological activities, and target membrane lipid composition remains elusive. Here we studied the antifungal effects of four Panax triterpene glycosides (ginsenosides) with sugar moieties at the C-3 (ginsenosides Rg3, Rh2), C-20 (compound K), and both (ginsenoside F2) positions in Saccharomyces cerevisiae mutants with altered sterol plasma membrane composition. We observed reduced cytostatic activity of the Rg3 and compound K in the UPC2-1 strain with high membrane sterol content. Moreover, LAM gene deletion reduced yeast resistance to Rg3 and digitonin, another saponin with glycosylated aglycon in the C-3 position. LAM genes encode plasma membrane-anchored StARkin superfamily-member sterol transporters. We also showed that the deletion of the ERG6 gene that inhibits ergosterol biosynthesis at the stage of zymosterol increased the cytostatic effects of Rg3 and Rh2, but not the other two tested ginsenosides. At the same time, in silico simulation revealed that the substitution of ergosterol with zymosterol in the membrane changes the spatial orientation of Rg3 and Rh2 in the membranes. These results imply that the plasma membrane sterol composition defines its interaction with triterpene glycoside depending on their glycoside group position. Our results also suggest that the biological role of membrane-anchored StARkin family protein is to protect eukaryotic cells from triterpenes glycosylated at the C-3 position.

Molecular and Cellular Mechanisms Underlying the Initiation and Progression of Alport Glomerular Pathology.

Alport syndrome results from a myriad of variants in the COL4A3, COL4A4, or COL4A5 genes that encode type IV (basement membrane) collagens. Unlike type IV collagen α1(IV)2α2(IV)1 heterotrimers, which are ubiquitous in basement membranes, α3/α4/α5 have a limited tissue distribution. The absence of these basement membrane networks causes pathologies in some, but not all these tissues. Primarily the kidney glomerulus, the stria vascularis of the inner ear, the lens, and the retina as well as a rare link with aortic aneurisms. Defects in the glomerular basement membranes results in delayed onset and progressive focal segmental glomerulosclerosis ultimately requiring the patient to undergo dialysis and if accessible, kidney transplant. The lifespan of patients with Alport syndrome is ultimately significantly shortened. This review addresses the consequences of the altered glomerular basement membrane composition in Alport syndrome with specific emphasis on the mechanisms underlying initiation and progression of glomerular pathology.

Critical Role of Caveolin-1 Loss/Dysfunction in Pulmonary Hypertension.

Pulmonary hypertension (PH) is a rare disease with a high morbidity and mortality rate. A number of systemic diseases and genetic mutations are known to lead to PH. The main features of PH are altered vascular relaxation responses and the activation of proliferative and anti-apoptotic pathways, resulting in pulmonary vascular remodeling, elevated pulmonary artery pressure, and right ventricular hypertrophy, ultimately leading to right heart failure and premature death. Important advances have been made in the field of pulmonary pathobiology, and several deregulated signaling pathways have been shown to be associated with PH. Clinical and experimental studies suggest that, irrespective of the underlying disease, endothelial cell disruption and/or dysfunction play a key role in the pathogenesis of PH. Endothelial caveolin-1, a cell membrane protein, interacts with and regulates several transcription factors and maintains homeostasis. Disruption of endothelial cells leads to the loss or dysfunction of endothelial caveolin-1, resulting in reciprocal activation of proliferative and inflammatory pathways, leading to cell proliferation, medial hypertrophy, and PH, which initiates PH and facilitates its progression. The disruption of endothelial cells, accompanied by the loss of endothelial caveolin-1, is accompanied by enhanced expression of caveolin-1 in smooth muscle cells (SMCs) that leads to pro-proliferative and pro-migratory responses, subsequently leading to neointima formation. The neointimal cells have low caveolin-1 and normal eNOS expression that may be responsible for promoting nitrosative and oxidative stress, furthering cell proliferation and metabolic alterations. These changes have been observed in human PH lungs and in experimental models of PH. In hypoxia-induced PH, there is no endothelial disruption, loss of endothelial caveolin-1, or enhanced expression of caveolin-1 in SMCs. Hypoxia induces alterations in membrane composition without caveolin-1 or any other membrane protein loss. However, caveolin-1 is dysfunctional, resulting in cell proliferation, medial hypertrophy, and PH. These alterations are reversible upon removal of hypoxia, provided there is no associated EC disruption. This review examined the role of caveolin-1 disruption and dysfunction in PH.

Leveraging Pseudomonas Stress Response Mechanisms for Industrial Applications.

Members of the genus Pseudomonas are metabolically versatile and capable of adapting to a wide variety of environments. Stress physiology of Pseudomonas strains has been extensively studied because of their biotechnological potential in agriculture as well as their medical importance with regards to pathogenicity and antibiotic resistance. This versatility and scientific relevance led to a substantial amount of information regarding the stress response of a diverse set of species such as Pseudomonas chlororaphis, P. fluorescens, P. putida, P. aeruginosa, and P. syringae. In this review, environmental and industrial stressors including desiccation, heat, and cold stress, are cataloged along with their corresponding mechanisms of survival in Pseudomonas. Mechanisms of survival are grouped by the type of inducing stress with a focus on adaptations such as synthesis of protective substances, biofilm formation, entering a non-culturable state, enlisting chaperones, transcription and translation regulation, and altering membrane composition. The strategies Pseudomonas strains utilize for survival can be leveraged during the development of beneficial strains to increase viability and product efficacy.

Comparative Study of Conventional and Fatty Acid Vesicular Systems – An Overview

: Fatty acid vesicles are suspensions of closed lipid bilayers that are composed of fatty acids and their ionized species which are restricted to a narrow pH range. The fatty acid molecules are oriented in such a way that their hydrocarbon tails are directed toward the membrane interior and the carboxyl groups are in contact with water. Recent innovations provide an opportunity to formulate fatty acid vesicles with distinguishing features such as extension of pH range, insensitivity toward divalent cations, easy alteration in membrane composition, very simple systems in terms of chemical nature and enhanced stability properties. This review contains detail about the present stature of fatty acid vesicles, comparative study of fatty acid vesicles with conventional liposomes, unique features of fatty acid vesicles (dynamicity, stability, matrix effect etc.,) and key evaluation parameters of fatty acid vesicles. Fatty acid vesicles were found to have high penetration capacity, good bio-distribution properties, increased diffusion rate and optimum drug deposition nature than other vesicular forms. They have various applications in transdermal delivery, follicular delivery and in brain targeting drug delivery systems (drugs that are unable to cross blood brain barrier due to high solubility). This review focuses on various researches conducted on fatty acid vesicles with reference to its formulation and evaluation parameters. © 2020 iGlobal Research and Publishing Foundation. All rights reserved.

Snx14 proximity labeling reveals a role in saturated fatty acid metabolism and ER homeostasis defective in SCAR20 disease

Fatty acids (FAs) are central cellular metabolites that contribute to lipid synthesis, and can be stored or harvested for metabolic energy. Dysregulation in FA processing and storage causes toxic FA accumulation or altered membrane compositions and contributes to metabolic and neurological disorders. Saturated lipids are particularly detrimental to cells, but how lipid saturation levels are maintained remains poorly understood. Here, we identify the cerebellar ataxia spinocerebellar ataxia, autosomal recessive 20 (SCAR20)-associated protein Snx14, an endoplasmic reticulum (ER)-lipid droplet (LD) tethering protein, as a factor required to maintain the lipid saturation balance of cell membranes. We show that following saturated FA (SFA) treatment, the ER integrity of SNX14KO cells is compromised, and both SNX14KO cells and SCAR20 disease patient-derived cells are hypersensitive to SFA-mediated lipotoxic cell death. Using APEX2-based proximity labeling, we reveal the protein composition of Snx14-associated ER-LD contacts and define a functional interaction between Snx14 and Δ-9 FA desaturase SCD1. Lipidomic profiling reveals that SNX14KO cells increase membrane lipid saturation following exposure to palmitate, phenocopying cells with perturbed SCD1 activity. In line with this, SNX14KO cells manifest delayed FA processing and lipotoxicity, which can be rescued by SCD1 overexpression. Altogether, these mechanistic insights reveal a role for Snx14 in FA and ER homeostasis, defects in which may underlie the neuropathology of SCAR20.

Cadmium stress dictates central carbon flux and alters membrane composition in Streptococcus pneumoniae

Metal ion homeostasis is essential for all forms of life. However, the breadth of intracellular impacts that arise upon dysregulation of metal ion homeostasis remain to be elucidated. Here, we used cadmium, a non-physiological metal ion, to investigate how the bacterial pathogen, Streptococcus pneumoniae, resists metal ion stress and dyshomeostasis. By combining transcriptomics, metabolomics and metalloproteomics, we reveal that cadmium stress dysregulates numerous essential cellular pathways including central carbon metabolism, lipid membrane biogenesis and homeostasis, and capsule production at the transcriptional and/or functional level. Despite the breadth of cellular pathways susceptible to metal intoxication, we show that S. pneumoniae is able to maintain viability by utilizing cellular pathways that are predominately metal-independent, such as the pentose phosphate pathway to maintain energy production. Collectively, this work provides insight into the cellular processes impacted by cadmium and how resistance to metal ion toxicity is achieved in S. pneumoniae.

Label-Free Imaging of Cholesterol Assemblies Reveals Hidden Nanomechanics of Breast Cancer Cells.

Tumor cells present profound alterations in their composition, structural organization, and functional properties. A landmark of cancer cells is an overall altered mechanical phenotype, which so far are linked to changes in their cytoskeletal regulation and organization. Evidence exists that the plasma membrane (PM) of cancer cells also shows drastic changes in its composition and organization. However, biomechanical characterization of PM remains limited mainly due to the difficulties encountered to investigate it in a quantitative and label‐free manner. Here, the biomechanical properties of PM of a series of MCF10 cell lines, used as a model of breast cancer progression, are investigated. Notably, a strong correlation between the cell PM elasticity and oncogenesis is observed. The altered membrane composition under cancer progression, as emphasized by the PM‐associated cholesterol levels, leads to a stiffening of the PM that is uncoupled from the elastic cytoskeletal properties. Conversely, cholesterol depletion of metastatic cells leads to a softening of their PM, restoring biomechanical properties similar to benign cells. As novel therapies based on targeting membrane lipids in cancer cells represent a promising approach in the field of anticancer drug development, this method contributes to deciphering the functional link between PM lipid content and disease.

3'quant mRNA-Seq of Porcine Liver Reveals Alterations in UPR, Acute Phase Response, and Cholesterol and Bile Acid Metabolism in Response to Different Dietary Fats.

Animal fats are considered to be unhealthy, in contrast to vegetable fats, which are rich in unsaturated fatty acids. However, the use of some fats, such as coconut oil, is still controversial. In our experiment, we divided experimental animals (domestic pigs) into three groups differing only in the type of fat used in the diet: group R: rapeseed oil (n = 5); group B: beef tallow (n = 5); group C: coconut oil (n = 6). After transcriptomic analysis of liver samples, we identified 188, 93, and 53 DEGs (differentially expressed genes) in R vs. B, R vs. C, and B vs. C comparisons, respectively. Next, we performed a functional analysis of identified DEGs with String and IPA software. We observed the enrichment of genes engaged in the unfolded protein response (UPR) and the acute phase response among genes upregulated in B compared to R. In contrast, cholesterol biosynthesis and cholesterol efflux enrichments were observed among genes downregulated in B when compared to R. Moreover, activation of the UPR and inhibition of the sirtuin signaling pathway were noted in C when compared to R. The most striking difference in liver transcriptomic response between C and B was the activation of the acute phase response and inhibition of bile acid synthesis in the latest group. Our results suggest that excessive consumption of animal fats leads to the activation of a cascade of mutually propelling processes harmful to the liver: inflammation, UPR, and imbalances in the biosynthesis of cholesterol and bile acids via altered organelle membrane composition. Nevertheless, these studies should be extended with analysis at the level of proteins and their function.