Debate over the electronic structure of CuIII complexes has intensified in recent years, focusing primarily on whether the [Cu(CF3)4]- moiety should be desc Show more
Debate over the electronic structure of CuIII complexes has intensified in recent years, focusing primarily on whether the [Cu(CF3)4]- moiety should be described as a classical Werner-type 3d8 CuIII complex or as a 3d10 CuI inverted ligand field framework. The copper periodate complex [Cu(HIO6)2]5-, discovered in 1937, has long been regarded as a 3d8 CuIII species and sometimes used as a reference 3d8 CuIII complex in oxidation state assignments for Cu-containing metalloenzymes. Nevertheless, its detailed electronic structure remains unexplored. Herein, we revisit the oxidation state of [Cu(HIO6)2]5- by means of X-ray photoelectron spectroscopy, X-ray absorption spectroscopy, and density functional theory calculations. The obtained results show that the oxidation state of the Cu center in [Cu(HIO6)2]5- lies at the boundary between the classical Werner-type and inverted ligand field regimes. This study thus demonstrates that categorizing the oxidation state of CuIII complexes as either 3d8 or 3d10 configurations is often inadequate; instead, the existence of electronic states at the boundary between these two limiting cases should be recognized. Show less
Abstract Imaging contrast agents are widely investigated in preclinical and clinical studies, among which biogenic imaging contrast agents (BICAs) are developing rapidly and playing an increasingly i Show more
Abstract Imaging contrast agents are widely investigated in preclinical and clinical studies, among which biogenic imaging contrast agents (BICAs) are developing rapidly and playing an increasingly important role in biomedical research ranging from subcellular level to individual level. The unique properties of BICAs, including expression by cells as reporters and specific genetic modification, facilitate various in vitro and in vivo studies, such as quantification of gene expression, observation of protein interactions, visualization of cellular proliferation, monitoring of metabolism, and detection of dysfunctions. Furthermore, in human body, BICAs are remarkably helpful for disease diagnosis when the dysregulation of these agents occurs and can be detected through imaging techniques. There are various BICAs matched with a set of imaging techniques, including fluorescent proteins for fluorescence imaging, gas vesicles for ultrasound imaging, and ferritin for magnetic resonance imaging. In addition, bimodal and multimodal imaging can be realized through combining the functions of different BICAs, which helps overcome the limitations of monomodal imaging. In this review, the focus is on the properties, mechanisms, applications, and future directions of BICAs. Show less
Abstract TFIIH is a 10āsubunit complex that regulates RNA polymerase II (pol II) transcription but also serves other important biological roles. Although much remains unknown about TFIIH function in Show more
Abstract TFIIH is a 10āsubunit complex that regulates RNA polymerase II (pol II) transcription but also serves other important biological roles. Although much remains unknown about TFIIH function in eukaryotic cells, much progress has been made even in just the past few years, due in part to technological advances (e.g. cryoEM and single molecule methods) and the development of chemical inhibitors of TFIIH enzymes. This review focuses on the major cellular roles for TFIIH, with an emphasis on TFIIH function as a regulator of pol II transcription. We describe the structure of TFIIH and its roles in pol II initiation, promoterāproximal pausing, elongation, and termination. We also discuss cellular roles for TFIIH beyond transcription (e.g. DNA repair, cell cycle regulation) and summarize small molecule inhibitors of TFIIH and diseases associated with defects in TFIIH structure and function. Show less
We developed an assay method for measuring dihydroorotate dehydrogenase (DHODH) activity in cultured HeLa cells and fibroblasts, and in stage III stomach cancer and adjacent normal tissues from the sa Show more
We developed an assay method for measuring dihydroorotate dehydrogenase (DHODH) activity in cultured HeLa cells and fibroblasts, and in stage III stomach cancer and adjacent normal tissues from the same patient. The assay comprised enzymatic reaction of DHODH with a large amount of dihydroorotic acid substrate, followed by fluorescence (FL) detection specific for orotic acid using the 4-trifluoromethyl-benzamidoxime fluorogenic reagent. The DHODH activities in the biologically complex samples were readily measured by the assay method. Our data indicate significantly higher DHODH activity in HeLa cells (340āĀ±ā25.9āpmol/105 cells/h) than in normal fibroblasts (54.1āĀ±ā7.40āpmol/105 cells/h), and in malignant tumour tissue (1.10āĀ±ā0.19ānmol/mg total proteins/h) than in adjacent normal tissue (0.24āĀ±ā0.11ānmol/mg total proteins/h). This is the first report that DHODH activity may be a diagnostic biomarker for cancer. Show less
Highly ordered interactions between immune and metabolic responses are evolutionarily conserved and paramount for tissue and organismal health. Disruption of these interactions underlies the emergence Show more
Highly ordered interactions between immune and metabolic responses are evolutionarily conserved and paramount for tissue and organismal health. Disruption of these interactions underlies the emergence of many pathologies, particularly chronic non-communicable diseases such as obesity and diabetes. Here, we examine decades of research identifying the complex immunometabolic signaling networks and the cellular and molecular events that occur in the setting of altered nutrient and energy exposures and offer a historical perspective. Furthermore, we describe recent advances such as the discovery that a broad complement of immune cells play a role in immunometabolism and the emerging evidence that nutrients and metabolites modulate inflammatory pathways. Lastly, we discuss how this work may eventually lead to tangible therapeutic advancements to promote health. Show less