OCTN1: A Widely Studied but Still Enigmatic Organic Cation Transporter Linked to Human Pathology and Drug Interactions

The Novel Organic Cation Transporter, OCTN1, is the first member of the OCTN subfamily; it belongs to the wider Solute Carrier family SLC22, which counts many members including cation and anion organic transporters. The tertiary structure has not been resolved for any cation organic transporter. The functional role of OCNT1 is still not well assessed despite the many functional studies so far conducted. The lack of a definitive identification of OCTN1 function can be attributed to the different experimental systems and methodologies adopted for studying each of the proposed ligands. Apart from the contradictory data, the international scientific community agrees on a role of OCTN1 in protecting cells and tissues from oxidative and/or inflammatory damage. Moreover, the involvement of this transporter in drug interactions and delivery has been well clarified, even though the exact profile of the transported/interacting molecules is still somehow confusing. Therefore, OCTN1 continues to be a hot topic in terms of its functional role and structure. This review focuses on the most recent advances on OCTN1 in terms of functional aspects, physiological roles, substrate specificity, drug interactions, tissue expression, and relationships with pathology.

Evolutionary Ecology of Natural Comammox Nitrospira Populations

Microbial species interact with each other and their environment (ecological processes) and undergo changes in their genomic repertoire over time (evolutionary processes). How these two classes of processes interact is largely unknown, especially for complex communities, as most studies of microbial evolutionary dynamics consider single species in isolation or a few interacting species in simplified experimental systems.

Experimental possibilities for industrial ventilation

The activity of evaluation and verification of industrial ventilation installations has a strong preventive role in terms of explosion risk mainly due to the fact that of the three determining elements that can lead to an explosion phenomenon, ventilation installations can determine the presence of two elements namely the presence of fuel (gases, vapours, dusts, mists) and the source of initiation (hot surface, flame, sparks of mechanical origin, electrical sparks, static electricity, etc.). The development of experimental systems on„ which particular hazardous aspects that may occur during the operation of industrial ventilation systems can be studied are vital to avoid dangerous situations in the current operation of ventilation installations. Knowledge of the dynamics of formation of explosive / toxic / asphyxiating environments is achieved by analysing explosive mixtures in relation to specific explosive intervals and is one of the most important priorities in ensuring optimal health and safety at work in industrial activities. The information obtained by analysing the dynamics of the formation of explosive / toxic / asphyxiating atmospheres is extremely useful for personnel responsible for health and safety at work, because with their help relevant decisions can be made to ensure safety and health conditions at the level of industrial premises. The paper presents an experimental equipment usable for the study of industrial ventilation systems.

Moiré Physics of One-Dimensional Related Systems and Their Measurement

Currently, the magic-angle graphene has given a tremendous boost to the study of unconventional superconductors. On the other hand, there were still limited experimental studies on superconductivity in one-dimensional (1D) carbon nanotube systems. The study of experimental systems in demonstrating superconductivity was therefore scientifically important. In this review, we have shown strategies toward demonstrating the superconductivity for the single double-wall carbon nanotube (DWCNT). In general, there have been two directions to analyse superconducting properties of one-dimensional materials: (i) strong correlated states (ii) anomalous electron transport operations. We introduced the transmission electron microscope (TEM) and Rayleigh scattering spectroscopy to describe the strong correlation. The theoretical foundations of moiré physics have also been described. Given all the methods, we concluded that the most intuitive way to demonstrate the superconductivity of single double-walled carbon nanotubes is the critical temperature. The sharp drop of the resistance could be directly observed, and the Tc could be obtained from the electrical transport data. In the last section, we also summarized the challenges that need to be addressed in future superconductivity studies of 1D carbon nanotubes.

FCC-ee overview: new opportunities create new challenges

With its high luminosity, its clean experimental conditions, and a range of energies that cover the four heaviest particles known today, FCC-ee offers a wealth of physics possibilities, with high potential for discoveries. The FCC-ee is an essential and complementary step towards a 100 TeV hadron collider, and as such offers a uniquely powerful combined physics program. This vision is the backbone of the 2020 European Strategy for Particle Physics. One of the main challenges is now to design experimental systems that can, demonstrably, fully exploit these extraordinary opportunities.

New Discoveries and Ambiguities of Nrf2 and ATF3 Signaling in Environmental Arsenic-Induced Carcinogenesis

Environment exposure to arsenic had been linked to increased incidents of human cancers. In cellular and animal experimental systems, arsenic has been shown to be highly capable of activating several signaling pathways that play critical roles in cell growth regulation, malignant transformation and the stemness of cancer stem-like cells. Emerging evidence indicates certain oncogenic properties of the Nrf2 transcription factor that can be activated by arsenic and many other environmental hazards. In human bronchial epithelial cells, our most recent data suggested that arsenic-activated Nrf2 signaling fosters metabolic reprogramming of the cells through shifting mitochondrial TCA cycle to cytosolic glycolysis, and some of the metabolites in glycolysis shunt the hexosamine biosynthesis and serine-glycine pathways important for the energy metabolism of the cancer cells. In the current report, we further demonstrated direct regulation of oncogenic signals by arsenic-activated Nrf2 and connection of Nrf2 with ATF3 stress transcription factor. Meanwhile, we also highlighted some unanswered questions on the molecular characteristics of the Nrf2 protein, which warrants further collaborative efforts among scientists for understanding the important role of Nrf2 in human cancers either associated or not to environmental arsenic exposure.

Gut Microbiota in Colorectal Cancer: Associations, Mechanisms, and Clinical Approaches

Colorectal cancer (CRC) is associated with the presence of particular gut microbes, as observed in many metagenomic studies to date. However, in most cases, it remains difficult to disentangle their active contribution to CRC from just a bystander role. This review focuses on the mechanisms described to date by which the CRC-associated microbiota could contribute to CRC. Bacteria like pks+ Escherichia coli, Fusobacterium nucleatum, or enterotoxigenic Bacteroides fragilis have been shown to induce mutagenesis, alter host epithelial signaling pathways, or reshape the tumor immune landscape in several experimental systems. The mechanistic roles of other bacteria, as well as newly identified fungi and viruses that are enriched in CRC, are only starting to be elucidated. Additionally, novel systems like organoids and organs-on-a-chip are emerging as powerful tools to study the direct effect of gut microbiota on healthy or tumor intestinal epithelium. Thus, the expanding knowledge of tumor-microbiota interactions holds promise for improved diagnosis and treatment of CRC. Expected final online publication date for the Annual Review of Cancer Biology, Volume 6 is April 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Kinetics of the Near Infrared Electrochemiluminescence from Metal Nanoclusters on Surface and in Solution

The electronics structures of some metal nanoclusters enable strong photoluminescence in the near infrared spectrum range. Activation of the luminescence via electrode reactions, rather than light source, i.e., electrochemiluminescence (ECL), has received growing interests due to the various potential benefits, but has been mostly limited to steady-state behaviors such as overall emission intensity and materials optimizations. Here, the ECL kinetics in representative experiments where nanoclusters as luminophores are either immobilized on the surface or free diffusing in solution were investigated based on classic theory. An analytical equation derived under a sequential mass transport limit regime quantitates the experimental ECL kinetics features in a wide range of conditions. Deconvolution of non-faradic charging current from redox current provides the threshold in time ranges for the analysis of ECL kinetics. The ECL kinetics profiles suggest that bimolecular or pseudo first order reactions limit the ECL generation immediately following the establishment of the applied potentials, while later ECL generation is governed by diffusion or mass transport displaying a Cottrell type decay over inverse square root time. Physical meanings of key parameters as defined in classic theorem are discussed in representative experimental systems for appropriate quantitation and evaluation of ECLs properties from different materials systems.

Developing an empirical model for spillover and emergence: Orsay virus host range in Caenorhabditis

A lack of tractable experimental systems in which to test hypotheses about the ecological and evolutionary drivers of disease spillover and emergence has limited our understanding of these processes. Here we introduce a promising system: Caenorhabditis hosts and Orsay virus, a positive-sense single-stranded RNA virus that naturally infects C. elegans. We assayed the susceptibility of species across the Caenorhabditis tree and found 21 of 84 wild strains belonging to 14 of 44 species to be susceptible to Orsay virus. Confirming patterns documented in other systems, we detected effects of host phylogeny on susceptibility. We then tested whether susceptible strains were capable of transmitting Orsay virus by transplanting exposed hosts and determining whether they transmitted infection to conspecifics during serial passage. We found no evidence of transmission in 10 strains (virus undetectable after passaging), evidence of low-level transmission in 5 strains (virus lost between passage 1 and 5), and evidence of sustained transmission in 6 strains (including all 3 experimental C. elegans strains). Transmission was associated with host phylogeny and with viral amplification in exposed populations. Variation in Orsay virus susceptibility and transmission among Caenorhabditis species suggests that the system could be powerful for studying spillover and emergence.

A genetic disorder reveals a hematopoietic stem cell regulatory network co-opted in leukemia

The molecular regulation of human hematopoietic stem cell (HSC) self-renewal is therapeutically important, but limitations in experimental systems and interspecies variation have constrained our knowledge of this process. Here, we have studied a rare genetic disorder due to MECOM haploinsufficiency, characterized by an early-onset absence of HSCs in vivo. By generating a faithful model of this disorder in primary human HSCs and coupling functional studies with integrative single-cell genomic analyses, we uncover a key transcriptional network involving hundreds of genes that is required for HSC self-renewal. Through our analyses, we nominate cooperating transcriptional regulators and identify how MECOM prevents the CTCF-dependent genome reorganization that occurs as HSCs exit quiescence. Strikingly, we show that this transcriptional network is co-opted in high-risk leukemias, thereby enabling these cancers to acquire stem cell properties. Collectively, we illuminate a regulatory network necessary for HSC self-renewal through the study of a rare experiment of nature.