We report a method that allows a complete quantitative characterization of whole single cells, assessing the total amount of carbon, nitrogen, oxygen, sodium, and magnesium and providing submicrometer maps of element molar concentration, cell density, mass, and volume. This approach allows quantifying elements down to 10(6) atoms/μm(3). This result was obtained by applying a multimodal fusion approach that combines synchrotron radiation microscopy techniques with off-line atomic force microscopy. The method proposed permits us to find the element concentration in addition to the mass fraction and provides a deeper and more complete knowledge of cell composition. We performed measurements on LoVo human colon cancer cells sensitive (LoVo-S) and resistant (LoVo-R) to doxorubicin. The comparison of LoVo-S and LoVo-R revealed different patterns in the maps of Mg concentration with higher values within the nucleus in LoVo-R and in the perinuclear region in LoVo-S cells. This feature was not so evident for the other elements, suggesting that Mg compartmentalization could be a significant trait of the drug-resistant cells.
A wide variety of biochemical reactions and physiological functions are known to require magnesium; nonetheless, its regulatory mechanisms (both at the cellular and systemic level) are still poorly characterised. Derangement of magnesium homeostasis is associated with several relevant human pathologies, e.g. diabetes, neuromuscular disorders, hypertension and other cardiovascular diseases. The study of the regulation of magnesium has gained particular interest in the last decades thanks to the molecular characterisation of specific magnesium transporters and the exploitation of molecular biology techniques to clarify their cellular and physiological function(s). In contrast, experimental tools to trace cellular magnesium and to define its homeostasis in living cells have not witnessed a corresponding progress. It was not until recently that efforts were paid to design more appropriate fluorescent indicators that could translate the advances of live imaging techniques into the field of magnesium research. Herein we critically summarise the state of the art in intracellular magnesium detection by fluorescent probes and focus on the need for improving methods and techniques in this area. We highlight the advantages of last-generation fluorescent indicators and discuss a number of challenges and opportunities that the development of novel and better sensors for magnesium still faces.
Thymidylate synthase (TS) is a target for pemetrexed and the prodrug 5-fluorouracil (5-FU) that inhibit the protein by binding at its active site. Prolonged administration of these drugs causes TS overexpression, leading to drug resistance. The peptide lead, LR (LSCQLYQR), allosterically stabilizes the inactive form of the protein and inhibits ovarian cancer (OC) cell growth with stable TS and decreased dihydrofolate reductase (DHFR) expression. To improve TS inhibition and the anticancer effect, we have developed 35 peptides by modifying the lead. The d-glutamine-modified peptide displayed the best inhibition of cisplatin-sensitive and -resistant OC cell growth, was more active than LR and 5-FU, and showed a TS/DHFR expression pattern similar to LR. Circular dichroism spectroscopy and molecular dynamics studies provided a molecular-level rationale for the differences in structural preferences and the enzyme inhibitory activities. By combining target inhibition studies and the modulation pattern of associated proteins, this work avenues a concept to develop more specific inhibitors of OC cell growth and drug leads.
The theory of logical gates in quantum computation has suggested new forms of quantum logic, called quantum computational logics. The basic semantic idea is the following: the meaning of a sentence is identified with a quregister (a system of qubits) or, more generally, with a mixture of quregisters (called qumix). In this framework, any sentence α of the language gives rise to a quantum tree: a kind of quantum circuit that transforms the quregister (qumix) associated to the atomic subformulas of α into the quregister (qumix) associated to α. A variant of the quantum computational semantics is represented by the quantum holistic semantics, which permits us to represent entangled meanings. Physical models of quantum computational logics can be built by means of Mach–Zehnder interferometers.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.