Scanning transmission X-ray microscopy (STXM) provides the imaging of biological specimens allowing the parallel collection of localized spectroscopic information by X-ray fluorescence (XRF) and/or ...X-ray Absorption Near Edge Spectroscopy (XANES). The complex metabolic mechanisms which can take place in biological systems can be explored by these techniques by tracing even small quantities of the chemical elements involved in the metabolic pathways. Here, we present a review of the most recent publications in the synchrotrons' scenario where soft X-ray spectro-microscopy has been employed in life science as well as in environmental research.
This
provides an updated overview on the involvement of phosphodiesterase (PDE) isoforms and of the corresponding inhibitors in neurological disorders, including dementia, Parkinson's disease, ...multiple sclerosis, neuropsychiatric conditions and cerebral ischemia. Particular attention has been dedicated to natural and semi-synthetic compounds. Translation into the clinic of preclinical results, toxicity profile and bioavailability represent the challenging aspects in the development of PDE inhibitors. With the aim of providing the latest updates to the reader, the 2023 contributions in the field were considered for the preparation of this
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Zeolites are porous minerals with high absorbency and ion-exchange capacity. Their molecular structure is a dense network of AlO
and SiO
that generates cavities where water and other polar molecules ...or ions are inserted/exchanged. Even though there are several synthetic or natural occurring species of zeolites, the most widespread and studied is the naturally occurring zeolite clinoptilolite (ZC). ZC is an excellent detoxifying, antioxidant and anti-inflammatory agent. As a result, it is been used in many industrial applications ranging from environmental remediation to oral applications/supplementation in vivo in humans as food supplements or medical devices. Moreover, the modification as micronization of ZC (M-ZC) or tribomechanically activated zeolite clinoptilolite (TMAZ) or furthermore as double tribomechanically activated zeolite clinoptilolite (PMA-ZC) allows improving its benefits in preclinical and clinical models. Despite its extensive use, many underlying action mechanisms of ZC in its natural or modified forms are still unclear, especially in humans. The main aim of this review is to shed light on the geochemical aspects and therapeutic potentials of ZC with a vision of endorsing further preclinical and clinical research on zeolites, in specific on the ZC and its modified forms as a potential agent for promoting human brain health and overall well-being.
Filamentous cable bacteria display long-range electron transport, generating electrical currents over centimeter distances through a highly ordered network of fibers embedded in their cell envelope. ...The conductivity of these periplasmic wires is exceptionally high for a biological material, but their chemical structure and underlying electron transport mechanism remain unresolved. Here, we combine high-resolution microscopy, spectroscopy, and chemical imaging on individual cable bacterium filaments to demonstrate that the periplasmic wires consist of a conductive protein core surrounded by an insulating protein shell layer. The core proteins contain a sulfur-ligated nickel cofactor, and conductivity decreases when nickel is oxidized or selectively removed. The involvement of nickel as the active metal in biological conduction is remarkable, and suggests a hitherto unknown form of electron transport that enables efficient conduction in centimeter-long protein structures.
This study aimed to assess the potential of a multidimensional approach to differentiate body hairs based on their physico-chemical properties and whether body hairs can replace the use of scalp hair ...in studies linked to forensic and systemic intoxication. This is the first case report controlling for confounding variables to explore the utility of multidimensional profiling of body hair using synchrotron synchrotron microbeam X-ray fluorescence (SR-XRF) for longitudinal and hair morphological region mapping) and benchtop methods, including attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) (complemented with chemometrics analysis), energy dispersive X-ray analysis (EDX) (complemented with heatmap analysis), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM) analysis (complemented by descriptive statistics) to profile different body hairs in terms of their elemental, biochemical, thermal, and cuticle properties. This multidimensional approach provided supportive information to emphasize the intricate and rather complex interplay between the organization and levels of elements and biomolecules within the crystalline and amorphous matrix of different body hairs responsible for the differences in physico-chemical properties between body hairs that are predominantly affected by the growth rate, follicle or apocrine gland activity, and external factors such as cosmetic use and exposure to environmental xenobiotics. The data from this study may have important implications for forensic science, toxicology and systemic intoxication, or other studies involving hair as a research matrix.
Scanning microscopies and spectroscopies like X-ray Fluorescence (XRF), Scanning Transmission X-ray Microscopy (STXM), and Ptychography are of very high scientific importance as they can be employed ...in several research fields. Methodology and technology advances aim at analysing larger samples at better resolutions, improved sensitivities and higher acquisition speeds. The frontiers of those advances are in detectors, radiation sources, motors, but also in acquisition and analysis software together with general methodology improvements. We have recently introduced and fully implemented an intelligent scanning methodology based on compressive sensing, on a soft X-ray microscopy beamline. This demonstrated sparse low energy XRF scanning of dynamically chosen regions of interest in combination with STXM, yielding spectroimaging data in the megapixel-range and in shorter timeframes than were previously not feasible. This research has been further developed and has been applied to scientific applications in biology. The developments are mostly in the dynamic triggering decisional mechanism in order to incorporate modern Machine Learning (ML) but also in the suitable integration of the method in the control system, making it available for other beamlines and imaging techniques. On the applications front, the method was previously successfully used on different samples, from lung and ovarian human tissues to plant root sections. This manuscript introduces the latest methodology advances and demonstrates their applications in life and environmental sciences. Lastly, it highlights the auxiliary development of a mobile application, designed to assist the user in the selection of specific regions of interest in an easy way.
Aging is a gradual process that occurs over time which leads to a progressive decline of cells and tissues. Telomere shortening, genetic instability, epigenetic alteration, and the accumulation of ...misfolded proteins represent the main hallmarks that cause perturbed cellular functions; this occurs in conjunction with the progression of the so-called "aging clocks". Rejuvenation aims to influence the natural evolution of such aging clocks and to enhance regenerative capacity, thus overcoming the limitations of common anti-aging interventions. Current rejuvenation processes are based on heterochronic parabiosis, cell damage dilution through asymmetrical cell division, the excretion of extracellular vesicles, the modulation of genetic instability involving G-quadruplexes and DNA methylation, and cell reprogramming using Yamanaka factors and the actions of antioxidant species. In this context, we reviewed the most recent contributions that report on small molecules acting as senotherapeutics; these molecules act by promoting one or more of the abovementioned processes. Candidate drugs and natural compounds that are being studied as potential rejuvenation therapies act by interfering with CDGSH iron-sulfur domain 2 (CISD2) expression, G-quadruplex structures, DNA methylation, and mitochondrial decay. Moreover, direct and indirect antioxidants have been reported to counteract or revert aging through a combination of mixed mechanisms.
Ferritinophagy is the process of autophagic degradation of ferritin that participates in the regulation of cellular iron homeostasis. This process was shown to be mediated by the selective ...cargo-receptor Nuclear Receptor Coactivator-4 (NCOA4) that binds ferritin and targets it to emerging autophagosome. To characterize some of the biochemical properties of the interaction between the two proteins we cloned and expressed in E. coli the ferritin-binding domain of human NCOA4, fragment 383–522. It was purified and subjected to biochemical analysis. The NCOA4(383–522) fragment was expressed in soluble and dimeric form, and CD spectra indicated low level of secondary structure. The Ferritin binding activity of the fragment was investigated by developing an electrophoretic mobility shift and an ELISA assays. They showed that the NCOA4 fragment binds the H-ferritin with an affinity in the nM range, but not the R23A H-ferritin mutant and the L-ferritin chain, confirming the high specificity for the H-chain. The H-ferritin could bind up to 24 NCOA4(383–522) fragments forming highly stable and insoluble complexes. The binding was partially inhibited only by Fe(II) among the various divalent metal ions analyzed. The iron-dependent, highly-specific formation of the remarkably stable H-ferritin-NCOA4 complex shown in this work may be important for the characterization of the mechanism of ferritinophagy.
•The recombinant ferritin binding domain of NCOA4 (residues 383-522) was expressed in E. coli and purified.•The domain binds ferritin H-chain with high affinity, but not its mutant Arg23Ala and ferritin L-chain•Electro mobility shift assay showed that H-ferritin binds up to 24 NCOA4 domains forming a highly stable complex•ELISA assay showed that the complex formation is partially inhibited by Fe(II) but not by other divalent metal ions.
As life expectancy increases, dementia affects a growing number of people worldwide. Besides current treatments, phosphodiesterase 9 (PDE9) represents an alternative target for developing innovative ...small molecules to contrast neurodegeneration. PDE inhibition promotes neurotransmitter release, amelioration of microvascular dysfunction, and neuronal plasticity. This review will provide an update on natural and nature-inspired PDE9 inhibitors, with a focus on the structural features of PDE9 that encourage the development of isoform-selective ligands. The expression in the brain, the presence within its structure of a peculiar accessory pocket, the asymmetry between the two subunits composing the protein dimer, and the selectivity towards chiral species make PDE9 a suitable target to develop specific inhibitors. Additionally, the world of natural compounds is an ideal source for identifying novel, possibly asymmetric, scaffolds, and xanthines, flavonoids, neolignans, and their derivatives are currently being studied. In this review, the available literature data were interpreted and clarified, from a structural point of view, taking advantage of molecular modeling: 3D structures of ligand-target complexes were retrieved, or built, and discussed.
Despite the rhizotoxicity of aluminum (Al) being identified over 100 years ago, there is still no consensus regarding the mechanisms whereby root elongation rate is initially reduced in the ...approximately 40% of arable soils worldwide that are acidic. We used high-resolution kinematic analyses, molecular biology, rheology, and advanced imaging techniques to examine soybean (Glycine max) roots exposed to Al. Using this multidisciplinary approach, we have conclusively shown that the primary lesion of Al is apoplastic. In particular, it was found that 75μM Al reduced root growth after only 5 min (or 30 min at 30μM Al), with Al being toxic by binding to the walls of outer cells, which directly inhibited their loosening in the elongation zone. An alteration in the biosynthesis and distribution of ethylene and auxin was a second, slower effect, causing both a transient decrease in the rate of cell elongation after 1.5 h but also a longer term gradual reduction in the length of the elongation zone. These findings show the importance of focusing on traits related to cell wall composition as well as mechanisms involved in wall loosening to overcome the deleterious effects of soluble Al.
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