Comparison of ESD and Conventional Methods in Single Cell Spray

Various inorganic ions are related to activity in a cell. Behavior of biological activity is traditionally observed by using optical microscope and/or MALDI. However, higher spatial resolution imaging technique is needed to observe organelles in a cell. In such cases, fixation in vacuum becomes quite big problem to maintain original structure in a cell. Rapid freezing seems one of the promising methods. But single cells cannot be treated as section. In this study, we devised a new rapid freezing method by combining electro-spray deposition and metal-touch freezing. In this method, individual cell is sprayed with a droplet emitted from the electro-spray tip, and each cells impact on the cooled metal surface, then frozen rapidly

Caring for Patients With Intractable Neurological Diseases

This is a qualitative descriptive study examining nurses’ attitudes about caring for patients with intractable neurological diseases, with a focus on dedication and conflicts. Semistructured interviews were conducted on 11 nurses with more than 5 years of clinical experience in addition to more than 3 years of experience in neurology wards. Senior nursing officers from each hospital selected the participants. In general, these nurses expressed distress over the inevitable progression of disease. Nurses talked about the “basis of dedication,” “conflicts with dedication,” “reorganization for maintaining dedication,” and “the reason for the change from conflict to commitment.” “Reorganization for maintaining dedication” meant that nurses were able to handle the prospect of rededicating themselves to their patients. Furthermore, “the reason for the change from conflict to commitment” referred to events that changed nurses’ outlooks on nursing care, their pride as nurses, or their learning experiences. They felt dedicated and conflicted both simultaneously and separately. While committing to their patients’ physical care, nurses were empowered to think positively and treat patients with dignity in spite of the care taking much time and effort, as well as entailing considerable risk

Bis-Silylation of Lu₃N@<i>I</i>_<i>h</i>‑C₈₀: Considerable Variation in the Electronic Structures

Photochemical reactions of Lu₃N@<i>I</i>_<i>h</i>-C₈₀ with disiliranes <b>1</b> and <b>2</b> produce several isomeric adducts. Spectroscopic analyses characterize the most stable isomers as 1,4(AA) adducts, which consist of paired twist conformers at rt. The electrochemical and theoretical studies reveal that the HOMO–LUMO energy gaps of the 1,4(AA) adducts are smaller than that of Lu₃N@<i>I</i>_<i>h</i>-C₈₀ because the electron-donating groups effectively raise the HOMO levels

Synthesis of Silylene-Bridged Endohedral Metallofullerene Lu₃N@<i>I</i>_<i>h</i>‑C₈₀

Functionalization of endohedral metallofullerenes has been shown to differ depending on photochemical or thermal pathways. We report that Lu₃N@<i>I</i>_<i>h</i>-C₈₀ reacts with thermally generated bis­(2,6-diethylphenyl)­silylene with high selectivity and forms monosilylated derivative <b>1b</b>. Unexpectedly, <b>1b</b> undergoes photochemical conversion to afford isomer <b>1a</b> under ambient light. These adducts were characterized using NMR, visible–near-IR spectroscopy, and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Single-crystal X-ray structure determination of <b>1a</b> reveals a rare example of an open 1,2-adduct at the [5,6]-ring junction of the <i>I</i>_<i>h</i>-C₈₀ cage. The electrochemical study reveals that the redox potentials of <b>1a</b> and <b>1b</b> are shifted cathodically compared to those of pristine Lu₃N@<i>I</i>_<i>h</i>-C₈₀ and that monosilylation is effective to fine-tune the electronic properties of endohedral metallofullerenes as well as empty fullerenes. Density functional theory calculations were also performed, which provide a theoretical basis for the structures and the behavior of the encapsulated Lu₃N cluster

Synthesis of Silylene-Bridged Endohedral Metallofullerene Lu₃N@<i>I</i>_<i>h</i>‑C₈₀

Functionalization of endohedral metallofullerenes has been shown to differ depending on photochemical or thermal pathways. We report that Lu₃N@<i>I</i>_<i>h</i>-C₈₀ reacts with thermally generated bis­(2,6-diethylphenyl)­silylene with high selectivity and forms monosilylated derivative <b>1b</b>. Unexpectedly, <b>1b</b> undergoes photochemical conversion to afford isomer <b>1a</b> under ambient light. These adducts were characterized using NMR, visible–near-IR spectroscopy, and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Single-crystal X-ray structure determination of <b>1a</b> reveals a rare example of an open 1,2-adduct at the [5,6]-ring junction of the <i>I</i>_<i>h</i>-C₈₀ cage. The electrochemical study reveals that the redox potentials of <b>1a</b> and <b>1b</b> are shifted cathodically compared to those of pristine Lu₃N@<i>I</i>_<i>h</i>-C₈₀ and that monosilylation is effective to fine-tune the electronic properties of endohedral metallofullerenes as well as empty fullerenes. Density functional theory calculations were also performed, which provide a theoretical basis for the structures and the behavior of the encapsulated Lu₃N cluster

Targeting cis-regulatory elements of FOXO family is a novel therapeutic strategy for induction of leukemia cell differentiation

Abstract Differentiation therapy has been proposed as a promising therapeutic strategy for acute myeloid leukemia (AML); thus, the development of more versatile methodologies that are applicable to a wide range of AML subtypes is desired. Although the FOXOs transcription factor represents a promising drug target for differentiation therapy, the efficacy of FOXO inhibitors is limited in vivo. Here, we show that pharmacological inhibition of a common cis-regulatory element of forkhead box O (FOXO) family members successfully induced cell differentiation in various AML cell lines. Through gene expression profiling and differentiation marker-based CRISPR/Cas9 screening, we identified TRIB1, a complement of the COP1 ubiquitin ligase complex, as a functional FOXO downstream gene maintaining an undifferentiated status. TRIB1 is direct target of FOXO3 and the FOXO-binding cis-regulatory element in the TRIB1 promoter, referred to as the FOXO-responsive element in the TRIB1 promoter (FRE-T), played a critical role in differentiation blockade. Thus, we designed a DNA-binding pharmacological inhibitor of the FOXO-FRE-T interface using pyrrole-imidazole polyamides (PIPs) that specifically bind to FRE-T (FRE-PIPs). The FRE-PIPs conjugated to chlorambucil (FRE-chb) inhibited transcription of TRIB1, causing differentiation in various AML cell lines. FRE-chb suppressed the formation of colonies derived from AML cell lines but not from normal counterparts. Administration of FRE-chb inhibited tumor progression in vivo without remarkable adverse effects. In conclusion, targeting cis-regulatory elements of the FOXO family is a promising therapeutic strategy that induces AML cell differentiation