Specific Molecular Species Research Articles

Prognostic significance of plasma molecular lipid species in coronary artery disease patients: A prospective cohort study

Abstract Background Circulating plasma lipids are vital indicators for quantifying coronary artery disease (CAD) risk, yet traditional biomarkers like LDL, HDL, and triglycerides often exhibit limited predictive capacity. Advancements in lipidomics have identified novel molecular constituents with the potential to improve prognostication in CAD patients. However, the prognostic value of lipidomics for long-term mortality has not yet been investigated. Objective In our study, which was part of the European Collaborative Project on Inflammation and Vascular Wall Remodeling in Atherosclerosis (ATHEROREMO), we aimed to investigate the predictive value of specific molecular lipid species for long-term mortality. Methods We utilized data from the 581 CAD patients enrolled in the ATHEROREMO clinical imaging study, who were admitted for either diagnostic coronary angiography or percutaneous coronary intervention. We measured a series of serum lipid species, comprising ceramides (Cer) and cholesteryl esters (CE), by mass spectrometry-based shotgun lipidomics. Long-term all-cause mortality follow-up was conducted in 2022 via the Civil Registry. We used the Kaplan-Meier method and multivariable Cox-proportional hazards regression (correction for age, sex, cardiac risk factors, statin use, hypercholesterolemia, and angiography indication) to assess survival distributions and associations with all-cause mortality. Results Mean age was 61.5 years (IQR: 53.5-61.5), 75% were male. A total of 55% patients were diagnosed with acute coronary syndrome (ACS) and 45% with stable angina pectoris (SAP). During a median follow-up of 11 years (IQR: 10.1-13.4) 179 patients died. Five molecular lipid species (two cholesteryl esters, one ceramide and two ceramide ratios) correlated with mortality (see Table). As an example, Figure 1 demonstrates a clear survival difference between patients with Cer(d18:1/16:0)/Cer(d18:1/24:0) ratio below versus above the median. Findings were consistent for ACS and SAP. Conclusion Our study demonstrates the prognostic value of specific cholesteryl esters, ceramides and ceramide ratios for 11-year mortality in patients with CAD. To the best of our knowledge, this is the longest follow-up study so far within this domain.Table.Lipid molecule and Mortality 11-yFig.1 Kaplan Meier Ceramide ratio

Methanol-to-Olefins Studied by UV Raman Spectroscopy as Compared to Visible Wavelength: Capitalization on Resonance Enhancement.

Resonance Raman spectroscopy can provide insights into complex reaction mechanisms by selectively enhancing the signals of specific molecular species. In this work, we demonstrate that, by changing the excitation wavelength, Raman bands of different intermediates in the methanol-to-hydrocarbons reactions can be identified. We show in particular how UV excitation enhances signals from short-chain olefins and cyclopentadienyl cations during the induction period, while visible excitation better detects later-stage aromatics. However, visible excitation is prone to fluorescence that can obscure Raman signals, and hence, we show how fast fluorescence rejection techniques like Kerr gating are necessary for extracting useful information from visible excitation measurements.

Comprehensive Clinical and Genetic Analyses of Circulating Bile Acids and Their Associations With Diabetes and Its Indices.

Bile acids (BAs) are cholesterol-derived compounds that regulate glucose, lipid, and energy metabolism. Despite their significance in glucose homeostasis, the association between specific BA molecular species and their synthetic pathways with diabetes mellitus (DM) is unclear. Here, we used a recently validated stable-isotope dilution highperformance liquid chromatography with tandem mass spectrometry (LC-MS/MS) method to quantify a panel of BAs in fasting plasma from subjects (n=2,145) and explored structural and genetic determinants of BAs linked to DM, insulin resistance and obesity. Multiple 12α-hydroxylated BAs were associated with DM [adjusted odds ratios (aORs):1.3-1.9 (all P<0.05)] and insulin resistance [aORs:1.3-2.2 (all P<0.05)]. Conversely, multiple 6a-hydroxylated BAs and isolithocholic acid (Iso-LCA) were inversely associated with DM and obesity [aORs:0.3-0.9 (all P<0.05)]. Genome-wide association studies (GWAS) revealed multiple genome-wide significant loci linked with nine of the 14 DM-associated BAs, including a locus for Iso-LCA (rs11866815). Mendelian randomization analyses showed genetically elevated DCA levels were causally associated with higher BMI, and Iso-LCA levels were causally associated with reduced BMI and DM risk. In conclusion, comprehensive large-scale quantitative mass spectrometry and genetics analyses show circulating levels of multiple structurally specific BAs, especially DCA and Iso-LCA, are clinically associated with and genetically linked to obesity and DM.

CRIRES-POP: A library of high resolution spectra in the near-infrared

Context. High-resolution spectra in the near-infrared (NIR) are an important tool for the detailed study of stellar atmospheres. The accurate identification of elements and molecules in these spectra can be used to determine chemical abundances and physical conditions in the photosphere of the observed star. Such identifications require precise line positions and strengths of both atomic and molecular features. Aims. This work focusses on the full identification of absorption lines in the NIR spectrum of the K-giant 10 Leo, including previously unidentified lines. The large number and complexity of the observed absorption lines require a deep search for potential spectral signatures to enable an unambiguous assignment to specific elements or molecular species. We aim to improve the published line lists of metals, some of which are determined by model calculations only, and many of which presently lack the completeness and accuracy of line parameters. Methods. The CRIRES-POP project provided high-resolution, high signal-to-noise ratio (S/N) spectra of several bright stars in the 1–5 μm range. For the K-giant 10 Leo, a spectrum corrected for telluric absorption and with precise wavelength calibration is available. This has been analysed by comparison with model spectra and up-to-date line lists. Results. We identified lines of 29 elements and eight molecular species. While the positions of many known lines could be confirmed, about 6% of all lines detected in 10 Leo could not be attributed to any known feature. For CO and its isotopologues, molecular constants could be derived and several additional lines identified. We report major inconsistencies for some prominent lines. In addition, abundances for several key elements in 10 Leo are provided.

Alterations in Circulating Bile Acids in Metabolic Dysfunction-Associated Steatotic Liver Disease: A Systematic Review and Meta-Analysis.

Background: Previous studies have suggested that bile acids (BAs) may participate in the development and/or progression of metabolic dysfunction-associated steatotic liver disease (MASLD). The present study aimed to define whether specific BA molecular species are selectively associated with MASLD development, disease severity, or geographic region. Methods: We comprehensively identified all eligible studies reporting circulating BAs in both MASLD patients and healthy controls through 30 July 2023. The pooled results were expressed as the standard mean difference (SMD) and 95% confidence interval (CI). Subgroup, sensitivity, and meta-regression analyses were performed to address heterogeneity. Results: Nineteen studies with 154,807 individuals were included. Meta-analysis results showed that total BA levels in MASLD patients were higher than those in healthy controls (SMD = 1.03, 95% CI: 0.63-1.42). When total BAs were divided into unconjugated and conjugated BAs or primary and secondary BAs, the pooled results were consistent with the overall estimates except for secondary BAs. Furthermore, we examined each individual BA and found that 9 of the 15 BAs were increased in MASLD patients, especially ursodeoxycholic acids (UDCA), taurococholic acid (TCA), chenodeoxycholic acids (CDCA), taurochenodeoxycholic acids (TCDCA), and glycocholic acids (GCA). Subgroup analysis revealed that different geographic regions or disease severities led to diverse BA profiles. Notably, TCA, taurodeoxycholic acid (TDCA), taurolithocholic acids (TLCA), and glycolithocholic acids (GLCA) showed a potential ability to differentiate metabolic dysfunction-associated steatohepatitis (MASH) (all p < 0.05). Conclusions: An altered profile of circulating BAs was shown in MASLD patients, providing potential targets for the diagnosis and treatment of MASLD.

The lipidomic correlates of epigenetic aging across the adult lifespan: A population-based study.

Lipid signaling is involved in longevity regulation, but which specific lipid molecular species affect human biological aging remains largely unknown. We investigated the relation between complex lipids and DNA methylation-based metrics of biological aging among 4181 participants (mean age 55.1 years (range 30.0-95.0)) from the Rhineland Study, an ongoing population-based cohort study in Bonn, Germany. The absolute concentration of 14 lipid classes, covering 964 molecular species and 267 fatty acid composites, was measured by Metabolon Complex Lipid Panel. DNA methylation-based metrics of biological aging (AgeAccelPheno and AgeAccelGrim) were calculated based on published algorithms. Epigenome-wide association analyses (EWAS) of biological aging-associated lipids and pathway analysis were performed to gain biological insights into the mechanisms underlying the effects of lipidomics on biological aging. We found that higher levels of molecular species belonging to neutral lipids, phosphatidylethanolamines, phosphatidylinositols, and dihydroceramides were associated with faster biological aging, whereas higher levels of lysophosphatidylcholine, hexosylceramide, and lactosylceramide species were associated with slower biological aging. Ceramide, phosphatidylcholine, and lysophosphatidylethanolamine species with odd-numbered fatty acid tail lengths were associated with slower biological aging, whereas those with even-numbered chain lengths were associated with faster biological aging. EWAS combined with functional pathway analysis revealed several complex lipids associated with biological aging as important regulators of known longevity and aging-related pathways.

Betaine lipids of Symbiodiniaceae hosted by Indo‐Pacific corals

SUMMARYThe total pool of coral lipids consists of lipids produced by both the coral host and its symbiotic dinoflagellates of the family Symbiodiniaceae. Betaine lipids (BL) are characteristic of plasma membranes of microalgae. Composition of such BL as 1,2‐diacylglyceryl‐3‐O‐carboxy‐(hydroxymethyl)‐choline (DGCC) that occur in coral symbionts may depend on either Symbiodiniaceae species or coral species. Membrane‐forming lipids DGCC have a zwitterion structure similar to that of phosphatidylcholine (PC). They can substitute for each other to a substantial extent, certainly in relation to membrane functions. In the present study, the profiles of DGCC and diacyl PC molecular species of symbiotic dinoflagellates from Acropora sp., Millepora platyphylla and Sinularia flexibilis were determined by high‐performance liquid chromatography with high‐resolution mass‐spectrometry. Colonies of Acropora sp. were characterized by higher contents of DGCC with eicosapentaenoic acid (20:5n‐3) and C28 polyunsaturated fatty acids; S. flexibilis, by a higher content of DGCC with palmitic acid (16:0); and M. platyphylla, by a higher content of DGCC with docosahexaenoic acid (22:6n‐3). Although the DGCC profile of the corals under study has distinctive features, it shows both similarities with and differences from the DGCC profiles of previously studied corals. Probably, each coral symbiont species has its own specific DGCC molecular species profile that is additionally modified in a certain way depending on environmental conditions created by the coral host. Molecular species DGCC and PC profiles were different. The most abundant PC molecular species were 16:0/22:5 and 38:4 in Acropora sp.; 39:5 and 38:4 in S. flexibilis; and 38:6, 16:0/22:5 and 18:0/22:6 in M. platyphylla. Thus, there is no clear evidence for any compensation or interchangeability between PC and DGCC.

Mass Spectrometry Analysis of the Human Brain Sphingolipidome.

In recent decades, mass spectrometry-based lipidomics has provided a fertile environment for scientific investigations of biochemical and mechanistic processes in biological systems. Notably, this approach has been used to characterize physiological and pathological processes relevant to the central nervous system by identifying changes in the sphingolipid content in the brain, cerebral spinal fluid, and blood plasma. However, despite a preponderance of studies identifying correlations between specific lipids and disease progression, this powerful resource has not yet substantively translated into clinically useful diagnostic assays. Part of this gap may be explained by insufficient depth of the lipidomic profiles in many studies, by lab-to-lab inconsistencies in methodology, and a lack of absolute quantification. These issues limit the identification of specific molecular species and the harmonization of results across independent studies. In this chapter, we contextualize these issues with recent reports identifying correlations between brain lipids and neurological diseases, and we describe the workflow our group has optimized for analysis of the blood plasma sphingolipidome, adapted to the characterization of the human brain tissue.

DGKα, Bridging Membrane Shape Changes with Specific Molecular Species of DAG/PA: Implications in Cancer and Immunosurveillance.

Cancer immunotherapy has revolutionized the oncology field. Despite the success, new molecular targets are needed to increase the percentage of patients that benefits from this therapy. Diacylglycerol kinase α (DGKα) has gathered great attention as a potential molecular target in immunotherapy because of its role in cancer proliferation and immunosuppression. DGKα catalyzes the ATP-dependent phosphorylation of diacylglycerol (DAG) to produce phosphatidic acid (PA). Since both lipids are potent signaling messengers, DGKα acts as a switch between different signaling pathways. Its role in cancer and immunosuppression has long been ascribed to the regulation of DAG/PA levels. However, this paradigm has been challenged with the identification of DGKα substrate acyl chain specificity, which suggests its role in signaling could be specific to DAG/PA molecular species. In several biological processes where DGKα plays a role, large membrane morphological changes take place. DGKα substrate specificity depends on the shape of the membrane that the enzyme binds to. Hence, DGKα can act as a bridge between large membrane morphological changes and the regulation of specific molecular species of DAG/PA. Bearing in mind the potential therapeutic benefits of targeting DGKα, here, the role of DGKα in cancer and T cell biology with a focus on the modulation of its enzymatic properties by membrane shape is reviewed. The goal is to contribute to a global understanding of the molecular mechanisms governing DGKα biology. This will pave the way for future experimentation and, consequently, the design of better, more potent therapeutic strategies aiming at improving the health outcomes of cancer patients.

The complete chloroplast genome of the medical plant Huperzia crispata from the Huperziaceae family: structure, comparative analysis, and phylogenetic relationships.

Huperzia crispata, belonging to the Huperziaceae family, is one of the most essential resources of huperzine A for candidate drugs to treat Alzheimer's diseases. However, there is very limited information about H. crispat, and its taxonomic status and interspecific relationships between Huperzia species are still unclear. To investigate the taxonomic classification of Huperzia species and identify species discrimination markers, the complete chloroplast (cp) genome of H. crispata was sequenced and characterized for the first time. Total genomic DNA was isolated and sequenced using the next-generation Illumina NovaSeq 6000 platform. The data were filtered, assembled and annotated by a series software and web service. The results were as follows: the cp genome of H. crispata was 154,320bp long with a large single-copy (LSC) region of 104,023bp, a small single-copy (SSC) region of 19,671bp, and a pair of inverted repeat (IRa and IRb) regions of 15,313bp. A total of 131 genes, including 87 protein-coding genes, 36 transfer RNA genes (tRNAs), and eight ribosome RNA genes (rRNAs), were annotated in the cp genome. The contraction and expansion of the inverted repeat (IR) regions were relatively conserved in the Huperzia genus. Codon usage bias analysis showed that the encoding rate at the 3-end of codon A/T (74.34%) was significantly higher than that of C/G (25.66%). A total of 8 hotspot loci with high Pi values (> 0.06) were identified in the four Huperzia species based on nucleic acid diversity analysis. Ka/Ks selective pressure analysis demonstrated that the cemA gene is the most common gene undergoing positive selection among Huperzia. In addition, a total of 261 simple sequence repeats and 179 interspersed repeats were identified in the cp genome. Phylogenetic tree analysis based on the complete protein sequences of 23 related species of H. crispata indicated thatH. serrataf. longipetiolata is a sister of H. crispata, suggesting that H. serrata f. longipetiolata and H. crispata are more closely related than H. serrata and H. lucidula. The results strongly supported that H. crispata was more closely related to H. serrata f. longipetiolata than to H. serrata and H. lucidula within the Huperzia genus. The outcome provided important information for the phylogenetic analysis of the subsequent specific molecular species identification in Huperzia. The present results will provide valuable information for further research into the classification, phylogeny and species identification of Huperzia plants.

Numerical study on the biosensing in mid-infrared based on multiple Fano-resonance plasmonic waveguide

In this article, the metal-insulator-metal based Fano resonance biosensors in mid-infrared are numerically investigated. The continuum states and discrete states of Fano resonances are produced by two asymmetric stubs and a symmetric ring, respectively. The quadruple Fano modes can be individually modulated for refractive index sensing in the mid-infrared spectral region (3–10 µm), which covering the characteristic infrared vibrations of specific molecular species. The maximum sensitivity and figure of merit is up to 7550 nm/RIU and 302, respectively. Moreover, the temperature sensing in ethanol and the concentration sensing in glucose solution indicate that the waveguide can not only quantify the temperature and concentration of the solution through the Fano resonance, but also characterize the chemical information of sample through the mid-infrared absorption. And the optimized MIM waveguide can effectively prevent the absorption of the aqueous solution disturbs the transmission spectrum and enhance the mid-infrared absorption of solvents. The excellent performances demonstrate the tunable multiple Fano resonance based on MIM waveguide is a promising method for biosensing in mid-infrared.

Abnormal male reproduction and embryonic development induced by downregulation of a phospholipid fatty acid-introducing enzyme Lpgat1 in zebrafish

Phospholipids in the membrane consist of diverse pairs of fatty acids bound to a glycerol backbone. The biological significance of the diversity, however, remains mostly unclear. Part of this diversity is due to lysophospholipid acyltransferases (LPLATs), which introduce a fatty acid into lysophospholipids. The human genome has 14 LPLATs and most of them are highly conserved in vertebrates. Here, we analyzed the function of one of these enzymes, lysophosphatidylglycerol acyltransferase 1 (Lpgat1), in zebrafish. We found that the reproduction of heterozygous (lpgat1+/−) male mutants was abnormal. Crosses between heterozygous males and wild-type females produced many eggs with no obvious cleavage, whereas eggs produced by crosses between heterozygous females and wild-type males cleaved normally. Consistent with this, spermatozoa from heterozygous males had reduced motility and abnormal morphology. We also found that the occurrence of lpgat1 homozygous (lpgat1−/−) mutants was far lower than expected. In addition, downregulation of lpgat1 by morpholino antisense oligonucleotides resulted in severe developmental defects. Lipidomic analysis revealed that selective phospholipid species with stearic acid and docosahexaenoic acid were reduced in homozygous larvae and spermatozoa from heterozygotes. These results suggest that the specific phospholipid molecular species produced by Lpgat1 have an essential role in sperm fertilization and in embryonic development.

Patterns of alpha-linolenic acid incorporation into phospholipids in H4IIE cells

Alpha linolenic acid (ALA) is an 18-carbon essential fatty acid found in plant-based foods and oils. While much attention has been placed on conversion of ALA to long chain polyunsaturated fatty acids, alternative routes of ALA metabolism exist and may lead to formation of other bioactive metabolites of ALA. The current study employed a non-targeted metabolomics approach to profile ALA metabolites that are significantly upregulated by ALA treatment. H4IIE hepatoma cells (n=3 samples per time point) were treated with 60 μM ALA or vehicle for 0, 0.25, 0.5, 1, 2, 3, 4, 6, 8, and 12 h. Samples were then extracted with methanol and analyzed using high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry. We observed selective changes in ALA incorporation into phospholipid classes and subclasses over the 12 h following ALA treatment. While levels of specific molecular species of ALA-containing phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and lysophospholipids were elevated with ALA treatment, others were not affected. Of the phospholipids that were increased, some (e.g., PC[18:3/18:1], PC[18:3/18:4], PE[18:3/18:2], PE[18:3/18:3]) were elevated almost immediately after exposure to ALA, while others [e.g., PE[18:1/18:3] PA[18:3/22:6], and PA[18:3/18:2]) were not elevated until several hours after ALA treatment. Overall, these results suggest that ALA incorporation into phospholipids is selective and support a metabolic hierarchy for ALA incorporation into specific phospholipids. Given the functionality of phospholipids based on their fatty acid composition, future studies will need to investigate the implications of ALA incorporation into specific phospholipids on cell function.

Simulation of Hydrogen Explosions in Closed or Vented Connected Vessels

ABSTRACT The aim of this work is to present an original numerical study of gaseous explosions with hydrogen in air inside a closed vessel and the chain propagation of an explosion in vented partitioned vessels. A fast calculation methodology, particularly interesting in the field of the risk assessment is developed mainly for lean mixtures. In addition to simulating the explosion in a closed environment, it takes into account the accidental transmission of the explosion from one compartment to another adjacent one by the means of the hot flow through the orifice common to both volumes. Finally, it is possible to generalize this novel methodology to a simple multi-partitioned structure. Some characteristics of the model have been initiated for the ignition and the combustion of propulsive powders in a one-compartment vessel and developed for gaseous mixtures with appropriate parameters linked to simplified kinetics. A simple representation of the combustion phenomena based on energy transfers and the action of specific molecular species is presented. The model allows the study of various parameters such as the initial thermodynamic conditions, the location of the ignition energy, and the size of the inner openings or the vent areas. The numerical results have been compared with data obtained by the means of experimental works in the laboratory or available in the literature and indicate correct preliminary trends.

Transmembrane transport in inorganic colloidal cell-mimics.

A key aspect of living cells is their ability to harvest energy from the environment and use it to pump specific atomic and molecular species in and out of their system-typically against an unfavourable concentration gradient1. Active transport allows cells to store metabolic energy, extract waste and supply organelles with basic building blocks at the submicrometre scale. Unlike living cells, abiotic systems do not have the delicate biochemical machinery that can be specifically activated to precisely control biological matter2-5. Here we report the creation of microcapsules that can be brought out of equilibrium by simple global variables (illumination and pH), to capture, concentrate, store and deliver generic microscopic payloads. Borrowing no materials from biology, our design uses hollow colloids serving as spherical cell-membrane mimics, with a well-defined single micropore. Precisely tunable monodisperse capsules are the result of a synthetic self-inflation mechanism and can be produced in bulk quantities. Inside the hollow unit, a photoswitchable catalyst6 produces a chemical gradient that propagates to the exterior through the membrane's micropore and pumps target objects into the cell, acting as a phoretic tractor beam7. An entropic energy barrier8,9 brought about by the micropore's geometry retains the cargo even when the catalyst is switched off. Delivery is accomplished on demand by reversing the sign of the phoretic interaction. Our findings provide a blueprint for developing the next generation of smart materials, autonomous micromachinery and artificial cell-mimics.

Sensing Molecules with Metal-Organic Framework Functionalized Graphene Transistors.

Graphene is inherently sensitive to vicinal dielectrics and local charge distributions, a property that can be probed by the position of the Dirac point in graphene field-effect transistors. Exploiting this as a useful sensing principle requires selectivity; however, graphene itself exhibits no molecule-specific interaction. Complementarily, metal-organic frameworks can be tailored to selective adsorption of specific molecular species. Here, a selective ethanol sensor is demonstrated by growing a surface-mounted metal-organic framework (SURMOF) directly onto graphene field-effect transistors (GFETs). Unprecedented shifts of the Dirac point, as large as 15V, are observed when the SURMOF/GFET is exposed to ethanol, while a vanishingly small response is observed for isopropanol, methanol, and other constituents of the air, including water. The synthesis and conditioning of the hybrid materials sensor with its functional characteristics are described and a model is proposed to explain the origin, magnitude, and direction of the Dirac point voltage shift. Tailoring multiple SURMOFs to adsorb specific gases on an array of such devices thus generates a versatile, selective, and highly sensitive platform for sensing applications.

Surface architecture of Neisseria meningitidis capsule and outer membrane as revealed by atomic force microscopy

An extensive morphological analysis of the Neisseria meningitidis cell envelope, including serogroup B capsule and outer membrane, based on atomic force microscopy (AFM) together with mechanical characterization by force spectroscopic measurements, has been carried out. Three meningococcal strains were used: the encapsulated serogroup B strain B1940, and the isogenic mutants B1940 siaD(+C) (lacking capsule), and B1940 cps (lacking both capsule and lipooligosaccharide outer core). AFM experiments with the encapsulated strain B1940 provided unprecedented images of the meningococcal capsule, which seems to be characterized by protrusions (“bumps”) with the lateral dimensions of about 30 nm. Measurement of the Young's modulus provided quantitative assessment of the property of the capsule to confer resistance to mechanical stress. Moreover, Raman spectroscopy gave a fingerprint by which it was possible to identify the specific molecular species of the three strains analyzed, and to highlight major differences between them.

Correlative nanoscopy: A multimodal approach to molecular resolution.

Atomic force microscopy (AFM) is a nano‐mechanical tool uniquely suited for biological studies at the molecular scale. AFM operation is based on mechanical interaction between the tip and the sample, a mechanism of contrast capable of measuring different information, including surface topography, mechanical, and electrical properties. However, the lack of specificity highlights the need to integrate AFM data with other techniques providing compositional hints. In particular, optical microscopes based on fluorescence as a mechanism of contrast can access the local distribution of specific molecular species. The coupling between AFM and super‐resolved fluorescence microscopy solves the resolution mismatch between AFM and conventional fluorescence optical microscopy. Recent advances showed that also the inherently label‐free imaging capabilities of the AFM are fundamental to complement the fluorescence images. In this review, we have presented a brief historical view on correlative microscopy, and, finally, we have summarized the progress of correlative AFM‐super‐resolution microscopy in biological research.

Physiological processes and lipidome dynamics in the soft coral Sinularia heterospiculata under experimental bleaching

Coral polyps host intracellular symbiotic dinoflagellates (SD). The loss of SD (referred as bleaching) under stressful environmental conditions is the main reason of coral reef destruction, and therefore, intensively studied over the world. Lipids are the structural base of biomembranes and energy reserve of corals and are directly involved in the coral bleaching. In order to establish a relationship between coral tissue morphology, physiological processes and lipidome dynamics during bleaching, the soft coral Sinularia heterospiculata was exposed to experimental heat stress (33°C) for 72h. A chlorophyll content, structure of cells, the level of reactive oxygen species (ROS), and molecular species of storage and structural lipids were analyzed. After 24h of heat exposure, the level of ROS-positive SD cells did not increase, but the host tissues lost a significant part of SD. The removal of SD cells by exocytosis were suggested. Exocytosis was presumed to prevail at earlier stages of the soft coral bleaching. Symbiophagosomes with degenerative SD were observed in the stressed coral host cells. After 24h, the content of phosphatidylinositols, which involved in apoptosis and autophagy, was significantly decreased. The innate immune response was triggered, and SD were digested by the coral host. After 48h, a degradation of SD chloroplasts and a decrease in the specific monogalactosyldiacylglycerol molecular species were detected that confirmed a disruption of lipid biosynthesis in chloroplasts. At the end of coral bleaching, the appearance of oxidized phosphatidylethanolamines, indicating damage to the host membranes, and the degradation of the coral tissues were simultaneously observed. Thus, a switch between dominant mechanisms of the SD loss during bleaching of S. heterospiculata was found and proved by certain variations of the lipidomic profile. Lipidomic parameters may become indicators of physiological processes occurring in the symbiotic coral organism and may be used for assessing anthropogenic or natural destructive effects on coral reefs.

α-Synuclein and neuronal membranes: Conformational flexibilities in health and disease

Parkinson’s disease (PD) is the second most common neurodegenerative disease. Currently, PD has no treatment. The neuronal protein α-synuclein (αS) plays an important role in PD. However, the molecular mechanisms governing its physiological and pathological roles are not fully understood. It is becoming widely acknowledged that the biological roles of αS involve interactions with biological membranes. In these biological processes there is a fine-tuned interplay between lipids affecting the properties of αS and αS affecting lipid metabolism, αS binding to membranes, and membrane damage. In this review, the intricate interactions between αS and membranes will be reviewed and a discussion of the relationship between αS and neuronal membrane structural plasticity in health and disease will be made. It is proposed that in healthy neurons the conformational flexibilities of αS and the neuronal membranes are coupled to assist the physiological roles of αS. However, in circumstances where their conformational flexibilities are decreased or uncoupled, there is a shift toward cell toxicity. Strategies to modulate toxic αS-membrane interactions are potential approaches for the development of new therapies for PD. Future work using specific αS molecular species as well as membranes with specific physicochemical properties should widen our understanding of the intricate biological roles of αS which, in turn, would propel the development of new strategies for the treatment of PD.