Baf-mediated transcriptional regulation of teashirt is essential for the development of neural progenitor cell lineages.

Accumulating evidence hints heterochromatin anchoring to the inner nuclear membrane as an upstream regulatory process of gene expression. Given that the formation of neural progenitor cell lineages and the subsequent maintenance of postmitotic neuronal cell identity critically rely on transcriptional regulation, it seems possible that the development of neuronal cells is influenced by cell type-specific and/or context-dependent programmed regulation of heterochromatin anchoring. Here, we explored this possibility by genetically disrupting the evolutionarily conserved barrier-to-autointegration factor (Baf) in the Drosophila nervous system.

Discovery of novel amidobenzimidazole derivatives as orally available small molecule modulators of stimulator of interferon genes for cancer immunotherapy.

Stimulator of interferon genes (STING) agonists show promise as immunomodulatory agents for cancer therapy. In this study, we report the discovery of a novel orally available STING agonist, SAP-04, that exhibits potent immunomodulatory effects for cancer therapy. By optimizing the amidobenzimidazole core with various pyridine-based heterocyclic substituents, we identified a monomeric variant that displayed more efficient STING agonistic activity than the corresponding dimer.

Effect of speech-stimulus degradation on phoneme-related potential.

Auditory evoked potential (AEP) has been used to evaluate the degree of hearing and speech cognition. Because AEP generates a very small voltage relative to ambient noise, a repetitive presentation of a stimulus, such as a tone, word, or short sentence, should be employed to generate ensemble averages over trials. However, the stimulation of repetitive short words and sentences may present an unnatural situation to a subject.

Development of Small-Molecule STING Activators for Cancer Immunotherapy.

In cancer immunotherapy, the cyclic GMP-AMP synthase-stimulator of interferon genes (STING) pathway is an attractive target for switching the tumor immunophenotype from 'cold' to 'hot' through the activation of the type I interferon response. To develop a new chemical entity for STING activator to improve cyclic GMP-AMP (cGAMP)-induced innate immune response, we identified KAS-08 via the structural modification of DW2282, which was previously reported as an anti-cancer agent with an unknown mechanism. Further investigation revealed that direct STING binding or the enhanced phosphorylation of STING and downstream effectors were responsible for DW2282-or KAS-08-mediated STING activity.

Block and Random Practice: A Wii Fit Dynamic Balance Training in Older Adults.

: To compare the effectiveness of blocked and random practice schedules of balance training in dynamic balance abilities of older adults using Wii Fit balance game tasks. : Forty-one participants who were not receiving hospice care or living in a nursing home participated. Three Wii Fit balance tasks (tasks A, B, and C) were selected for training, and one task (task D) was selected as the transfer test among the nine tasks in the Wii Fit balance game software.

Mitochondrial dysfunction and activation of iNOS are responsible for the palmitate-induced decrease in adiponectin synthesis in 3T3L1 adipocytes.

Mitochondrial dysfunction and endoplasmic reticulum (ER) stress are considered the key determinants of insulin resistance. Impaired mitochondrial function in obese animals was shown to induce the ER stress response, resulting in reduced adiponectin synthesis in adipocytes. The expression of inducible nitric oxide synthase (iNOS) is increased in adipose tissues in genetic and dietary models of obesity.

NF-kappaB activation in hypothalamic pro-opiomelanocortin neurons is essential in illness- and leptin-induced anorexia.

Anorexia and weight loss are prevalent in infectious diseases. To investigate the molecular mechanisms underlying these phenomena, we established animal models of infection-associated anorexia by administrating bacterial and viral products, lipopolysaccharide (LPS) and human immunodeficiency virus-1 transactivator protein (Tat). In these models, we found that the nuclear factor-kappaB (NF-kappaB), a pivotal transcription factor for inflammation-related proteins, was activated in the hypothalamus.

Does the mitral annulus shrink or enlarge during systole? A real-time 3D echocardiography study.

This study was conducted to explore the geometrical changes of the mitral annulus during systole. The 3D shape of the mitral annulus was reconstructed in 13 normal subjects who had normal structure of the mitral apparatus using real-time 3D echocardiography (RT3DE) and 3D computer software. The two orthogonal (antero-posterior and commissure-commissure) dimensions, the areas (2D projected and 3D surface) and the non-planarity of the mitral annulus were estimated during early, mid and late systole.

Essential role of mitochondrial function in adiponectin synthesis in adipocytes.

Objective: Adiponectin is an important adipocytokine that improves insulin action and reduces atherosclerotic processes. The plasma adiponectin level is paradoxically reduced in obese individuals, but the underlying mechanism is unknown. This study was undertaken to test the hypothesis that mitochondrial function is linked to adiponectin synthesis in adipocytes.

3D geometry of a normal tricuspid annulus during systole: a comparison study with the mitral annulus using real-time 3D echocardiography.

Aim: This study was done to explore the 3D geometry of the normal tricuspid annulus and compare it with the mitral annulus (MA), using real-time 3D echocardiography (RT3DE) and newly developed 3D computer software.

Methods: Thirteen left ventricular (LV) and 13 right ventricular (RV) volumetric images were obtained using RT3DE from normal subjects. LV and RV volumetric data were segmented into 16 rotational apical planes (angle increment=11.

Assessment of left ventricular asynchrony using volume-time curves of 16 segments by real-time 3 dimensional echocardiography: comparison with tissue Doppler imaging.

Background: Recent technical developments with high-resolution real-time 3 dimensional echocardiography (RT3DE) facilitate the acquisition of high quality images and the analysis of segmental volume-time curves (VTCs).

Aims: To assess left ventricular (LV) asynchrony using the VTCs of 16 segments by RT3DE, and to evaluate accuracy compared to tissue Doppler imaging (TDI).

Methods: Twenty-three heart failure (HF) patients (LVEF: 25+/-6%, age: 60+/-13 years) and 16 normal controls underwent TDI and RT3DE.

CCAAT/enhancer-binding protein delta activates the Runx2-mediated transcription of mouse osteocalcin II promoter.

CCAAT/enhancer-binding proteins (C/EBPs) are involved in the regulation of cell proliferation, differentiation, and control of metabolic function. Although the roles of C/EBPs in osteoblasts are largely unknown, both C/EBPbeta and -delta have been shown to enhance rat osteocalcin promoter activity through the synergistic activation of Runx2 at the C/EBP element. Here we show that in the mouse, C/EBPdelta increases the expression of osteocalcin whereas C/EBPbeta does not.

AMPK activation increases fatty acid oxidation in skeletal muscle by activating PPARalpha and PGC-1.

AMP-activated protein kinase (AMPK) activation increases fatty acid oxidation in skeletal muscle by decreasing malonyl CoA concentrations. However, this may not explain the long-term effects of AMPK activation. Here we show that AMPK activation by 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) increases mRNA expression of PPARalpha target genes and PGC-1 in cultured muscle cells and mouse skeletal muscle, and that inhibition of PPARalpha and PGC-1 by siRNAs prevents AICAR-stimulated increase in fatty acid oxidation.

Activation of peroxisome proliferator-activated receptor-gamma inhibits the Runx2-mediated transcription of osteocalcin in osteoblasts.

Mesenchymal cells are able to differentiate into several distinct cell types, including osteoblasts and adipocytes. The commitment to a particular lineage may be regulated by specific transcription factors. Peroxisome proliferator-activated receptor-gamma (PPARgamma), acting in conjunction with CCAAT/enhancer-binding protein-alpha, has been suggested as a key regulator of adipogenic differentiation.