Atomic Imaging and Thermally Induced Dynamic Structural Evolution of Two-Dimensional CrS.

In this study, facile salt-assisted chemical vapor deposition (CVD) was used to synthesize ultrathin non-van der Waals chromium sulfide (CrS) with a thickness of ∼1.9 nm. The structural transformation of as-grown CrS was studied using advanced heating techniques combined with transmission electron microscopy (TEM).

Diffused Beam Energy to Dope van der Waals Electronics and Boost Their Contact Barrier Lowering.

Contact engineering of two-dimensional semiconductors is a central issue for performance improvement of micro-/nanodevices based on these materials. Unfortunately, the various methods proposed to improve the Schottky barrier height normally require the use of high temperatures, chemical dopants, or complex processes. This work demonstrates that diffused electron beam energy (DEBE) treatment can simultaneously reduce the Schottky barrier height and enable the direct writing of electrical circuitry on van der Waals semiconductors.

In Situ Atomic-Scale Observation of Monolayer MoS Devices under High-Voltage Biasing via Transmission Electron Microscopy.

2D materials have great potential for not only device scaling but also various applications. To prompt the development of 2D electronics and optoelectronics, a better understanding of the limitation of materials is essential. Material failure caused by bias can lead to variations in device behavior and even electrical breakdown.

Atomic-Scale Fabrication of In-Plane Heterojunctions of Few-Layer MoS via In Situ Scanning Transmission Electron Microscopy.

Layered MoS is a prospective candidate for use in energy harvesting, valleytronics, and nanoelectronics. Its properties strongly related to its stacking configuration and the number of layers. Due to its atomically thin nature, understanding the atomic-level and structural modifications of 2D transition metal dichalcogenides is still underdeveloped, particularly the spatial control and selective precision.

A novel, de novo mutation in the gene: infantile-onset phenotype and the signaling pathway involved.

encodes the γ-subunit isoform of 5'-AMP-activated protein kinase (AMPK), a heterotrimeric enzyme with major roles in the regulation of energy metabolism in response to cellular stress. Mutations in have been implicated in a unique hypertrophic cardiomyopathy (HCM) characterized by cardiac glycogen overload, ventricular preexcitation, and hypertrophy. We identified a novel, de novo mutation (K475E) in a neonate with prenatal onset of HCM.

Metformin protects cardiomyocyte from doxorubicin induced cytotoxicity through an AMP-activated protein kinase dependent signaling pathway: an in vitro study.

Doxorubicin (Dox) is one of the most widely used antitumor drugs, but its cumulative cardiotoxicity have been major concerns in cancer therapeutic practice for decades. Recent studies established that metformin (Met), an oral anti-diabetic drug, provides protective effects in Dox-induced cardiotoxicity. Met has been shown to increase fatty acid oxidation, an effect mediated by AMP activated protein kinase (AMPK).

HE4 (WFDC2) gene overexpression promotes ovarian tumor growth.

Selective overexpression of Human epididymal secretory protein E4 (HE4) points to a role in ovarian cancer tumorigenesis but little is known about the role the HE4 gene or the gene product plays. Here we show that elevated HE4 serum levels correlate with chemoresistance and decreased survival rates in EOC patients. HE4 overexpression promoted xenograft tumor growth and chemoresistance against cisplatin in an animal model resulting in reduced survival rates.

In vitro silencing of the insulin receptor attenuates cellular accumulation of fibronectin in renal mesangial cells.

Background: Insulin receptor (InsR) and insulin signaling proteins are widely distributed throughout the kidney cortex. Insulin signaling can act in the kidney in multiple ways, some of which may be totally independent of its primary role of the maintenance of whole-body glucose homeostasis. However, descriptions of the insulin signaling in renal glomerular mesangial cells (MCs) are quite limited and the roles of insulin signaling in MC functions have not been sufficiently elucidated.

Exercise training and PI3Kα-induced electrical remodeling is independent of cellular hypertrophy and Akt signaling.

In contrast with pathological hypertrophy, exercise-induced physiological hypertrophy is not associated with electrical abnormalities or increased arrhythmia risk. Recent studies have shown that increased cardiac-specific expression of phosphoinositide-3-kinase-α (PI3Kα), the key mediator of physiological hypertrophy, results in transcriptional upregulation of ion channel subunits in parallel with the increase in myocyte size (cellular hypertrophy) and the maintenance of myocardial excitability. The experiments here were undertaken to test the hypothesis that Akt1, which underlies PI3Kα-induced cellular hypertrophy, mediates the effects of augmented PI3Kα signaling on the transcriptional regulation of cardiac ion channels.

β-Adrenergic receptor-PI3K signaling crosstalk in mouse heart: elucidation of immediate downstream signaling cascades.

Sustained β-adrenergic receptors (βAR) activation leads to cardiac hypertrophy and prevents left ventricular (LV) atrophy during LV unloading. The immediate signaling pathways downstream from βAR stimulation, however, have not been well investigated. The current study was to examine the early cardiac signaling mechanism(s) following βAR stimulation.

Effect of disruption of Akt-1 of lin(-)c-kit(+) stem cells on myocardial performance in infarcted heart.

Aims: We have demonstrated an important role of bone marrow-derived stem cells in preservation of myocardial function. We investigated whether Akt-1 of lin(-)c-kit(+) stem cells preserves ventricular function following myocardial infarction (MI).

Methods And Results: Isolated lin(-)c-kit(+) cells were conjugated with anti-c-kit heteroconjugated to anti-vascular cell adhesion molecule to facilitate the attachment of stem cells into damaged tissues.

High ambient glucose induces angiotensin-independent AT-1 receptor activation, leading to increases in proliferation and extracellular matrix accumulation in MES-13 mesangial cells.

Diabetic nephropathy is associated with mesangial ECM (extracellular matrix) accumulation. We have shown that AT-1R [Ang II (angiotensin II) type I receptor] signalling induces ECM proteins via transactivation of PI3K (phosphoinositide 3-kinase) in mesangial cells. In the present study, we examined the mechanisms underlying the effect of high ambient glucose on cell proliferation and ECM expansion in a mesangial context.

Temporally controlled overexpression of cardiac-specific PI3Kalpha induces enhanced myocardial contractility--a new transgenic model.

The phosphatidylinositol 3-kinase (PI3K) signaling pathway regulates multiple cellular processes including cell survival/apoptosis and growth. In the cardiac context, PI3Kalpha plays important roles in cardiac growth. We have shown that cardiac PI3K activity is highly regulated during development, with the highest levels found during the fetal-neonatal transition period and the lowest levels in the adult.

Beta-adrenergic receptor mediated protection against doxorubicin-induced apoptosis in cardiomyocytes: the impact of high ambient glucose.

Recent studies have demonstrated that the beta2-adrenergic receptor (beta2AR)-Galphai signaling pathway exerts a cardiac antiapoptotic effect. The goals of this study were to determine the intracellular signaling factors involved in beta2AR-mediated protection against doxorubicin-induced apoptosis in H9c2 cardiomyocyte and explore the impact of high ambient glucose on the antiapoptotic effect. Under physiological glucose environment (100 mg/dl), beta2AR stimulation prevented doxorubicin-induced apoptosis, which was attenuated by cotreatment with wortmannin, a phosphoinositide 3-kinase (PI3K) inhibitor, or transfection of a dominant-negative Akt.

A novel phosphoinositide 3-kinase-dependent pathway for angiotensin II/AT-1 receptor-mediated induction of collagen synthesis in MES-13 mesangial cells.

Chronic activation of the angiotensin II (ANG II) type 1 receptor (AT-1R) is critical in the development of chronic kidney disease. ANG II activates mesangial cells (MCs) and stimulates the synthesis of extracellular matrix components. To determine the molecular mechanisms underlying the induction of MC collagen, a mouse mesangial cell line MES-13 was employed.

A novel signaling pathway for beta-adrenergic receptor-mediated activation of phosphoinositide 3-kinase in H9c2 cardiomyocytes.

Stimulation of cardiac beta-adrenergic receptors (beta-AR) activates both the G(s)- and G(i)-coupled signaling cascades, including the phosphoinositide 3 kinase (PI3K) pathway, that have important physiological implications. Multiple isoforms of PI3K exist in the heart. The goals of this study were to examine the intracellular signaling pathways linking beta-AR to PI3K and to identify the PI3K isoform mediating this transactivation in a cardiac context.

Ontogeny of phosphoinositide 3-kinase signaling in developing heart: effect of acute beta-adrenergic stimulation.

Signaling pathways underlying transition of cardiomyocyte growth from hyperplasia in fetal/newborn to hypertrophy in postnatal/adult hearts are not well understood. We have shown that beta-adrenergic receptor (beta-AR)-mediated regulation of neonatal cardiomyocyte proliferation involves p70 ribosomal protein S6 kinase (p70S6K). Here we examined the ontogeny of phosphoinositide 3-kinase (PI3K)/p70S6K signaling pathway in rat hearts and investigated the influence of beta-AR on this pathway during development.

Evidence for cyclin D3 as a novel target of rapamycin in human T lymphocytes.

The immunosuppressant rapamycin has been shown to inhibit G(1)/S transition of the cell cycle. This inhibition is thought to be mediated by maintenance of the threshold levels of cyclin-dependent kinase (CDK) inhibitor p27(Kip1) (p27) and inhibition of p70 s6 kinase (p70(s6k)). However, recent evidence suggests that cells still remain sensitive to rapamycin in the absence of functional p27 or p70(s6k).

Regulation of cardiac beta 1-adrenergic receptor transcription during the developmental transition.

The beta(1)-adrenergic receptor (beta(1)AR) gene contains binding sites for myc/max proteins within a glucocorticoid response element. Transcriptional activation of the beta(1)AR is the result of cooperative binding between c-myc and the glucocorticoid receptor on the beta(1)AR promoter. The transcriptional regulation of both beta(1)AR and c-myc are developmentally regulated.

Molecular interactions between glucocorticoid and catecholamine signaling pathways.

To study the mechanism underlying glucocorticoid regulation of the beta(1)-adrenergic receptor (beta(1)AR), we identified a 43-bp region (-1274 to -1232 from the translation start site) that contains a novel glucocorticoid regulatory unit (GRU) that confers glucocorticoid responsiveness. The sequence encompassing the GRU is (5')TAATTA(3'), which is a core-binding motif for the homeodomain proteins; an E-box ((5')CACGTG(3')) binding site for the Myc/Max family proteins, and an overlapping glucocorticoid response element half-site ((5')TGTTCT(3')). We showed that the half-site is critical for GRU-protein interactions, which also require binding of proteins to the E-box and the homeodomain region.