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FOXO1 Activates Glutamine Synthetase Gene in Mouse Skeletal Muscles through a Region Downstream of 3'-UTR; Possible Contribution to Ammonia Detoxification
Skeletal muscle is a reservoir of energy in the form of protein, which is degraded under catabolic conditions, resulting in the formation of amino acids and ammonia as a by-product. The expression of FOXO1, a forkhead-type transcription factor, increases during starvation and exercise. In agreement, transgenic FOXO1-Tg mice that overexpress FOXO1 in skeletal muscle exhibit muscle atrophy. The a...


Testosterone alters Iron metabolism and Stimulates Red Cell Production Independently of Dihydrotestosterone
Testosterone (T) stimulates erythropoiesis and regulates iron homeostasis. However, it remains unknown whether the (type II) 5α-reduction of T to dihydrotestosterone (DHT) mediates these androgenic effects, as it does in some other tissues. Our purpose was to determine whether inhibition of type II 5α-reductase (via finasteride) alters red blood cell (RBC) production and serum marke...
Effects of Delayed Gastric Emptying on Postprandial Glucose Kinetics, Insulin Sensitivity and Beta Cell Function
Controlling meal related glucose excursions continue to be a therapeutic challenge in diabetes mellitus. Mechanistic reasons for this need to be understood better to develop appropriate therapies. To investigate delayed gastric emptying effects on postprandial glucose turnover, insulin sensitivity and beta cell responsivity and function, as a feasibility study prior to studying patients with ty...


(Pro)renin Receptor in the Skeletal Muscle is Involved in the Development of Insulin Resistance Associated with Post-Infarct Heart Failure in Mice
We previously reported that insulin resistance was induced by the impairment of insulin signaling in the skeletal muscle from heart failure (HF) via NAD(P)H oxidase-dependent oxidative stress. (Pro)renin receptor ((P)RR) is involved in the activation of local renin-angiotensin system and subsequent oxidative stress. We thus examined whether (P)RR inhibitor, handle-region peptide (HRP), could am...
Activation of growth hormone secretagogue receptor induces time-dependent clock phase delay in mice
Early studies have reported a phase-shifting effect of growth hormone secretagogues (GHSs). This study aimed to determine the mechanism of action of GHSs. We examined the response of the hypothalamic suprachiasmatic nuclei (SCN) to growth hormone releasing peptide-6 (GHRP-6) by assessing effects on the phase of locomotor activity rhythms, SCN neuronal discharges, and the potential signaling pat...


Subcellular optogenetic inhibition of G proteins generates signaling gradients and cell migration
Cells sense gradients of extracellular cues and generate polarized responses such as cell migration and neurite initiation. There is static information on the intracellular signaling molecules involved in these responses, but how they dynamically orchestrate polarized cell behaviors is not well understood. A limitation has been the lack of methods to exert spatial and temporal control over spec...
Role of TGF-beta receptor III localization in polarity and breast cancer progression
The majority of breast cancers originate from the highly polarized luminal epithelial cells lining the breast ducts. However, cell polarity is often lost during breast cancer progression. The type III transforming growth factor-β cell surface receptor (TβRIII) functions as a suppressor of breast cancer progression and also regulates the process of epithelial-to-mesenchymal transition ...

Common regulatory control of CTP synthase enzyme activity and filament formation
The ability of enzymes to assemble into visible supramolecular complexes is a widespread phenomenon. Such complexes have been hypothesized to play a number of roles; however, little is known about how the regulation of enzyme activity is coupled to the assembly/disassembly of these cellular structures. CTP synthase is an ideal model system for addressing this question because its activity is re...
Kinetochore-microtubule attachment throughout mitosis potentiated by the elongated stalk of the kinetochore kinesin CENP-E
Centromere protein E (CENP-E) is a highly elongated kinesin that transports pole-proximal chromosomes during congression in prometaphase. During metaphase, it facilitates kinetochore–microtubule end-on attachment required to achieve and maintain chromosome alignment. In vitro CENP-E can walk processively along microtubule tracks and follow both growing and shrinking microtubule plus ends....

HSP70-binding protein HSPBP1 regulates chaperone expression at a posttranslational level and is essential for spermatogenesis
Molecular chaperones play key roles during growth, development, and stress survival. The ability to induce chaperone expression enables cells to cope with the accumulation of nonnative proteins under stress and complete developmental processes with an increased requirement for chaperone assistance. Here we generate and analyze transgenic mice that lack the cochaperone HSPBP1, a nucleotide-excha...
Cdk1 promotes cytokinesis in fission yeast through activation of the septation initiation network
In Schizosaccharomyces pombe, late mitotic events are coordinated with cytokinesis by the septation initiation network (SIN), an essential spindle pole body (SPB)–associated kinase cascade, which controls the formation, maintenance, and constriction of the cytokinetic ring. It is not fully understood how SIN initiation is temporally regulated, but it depends on the activation of the GTPas...

Genome-wide analysis of Saccharomyces cerevisiae identifies cellular processes affecting intracellular aggregation of Alzheimer's amyloid-beta42: importance of lipid homeostasis
Amyloid-β (Aβ)–containing plaques are a major neuropathological feature of Alzheimer's disease (AD). The two major isoforms of Aβ peptide associated with AD are Aβ40 and Aβ42, of which the latter is highly prone to aggregation. Increased presence and aggregation of intracellular Aβ42 peptides is an early event in AD progression. Improved understanding of cell...
OS-9 facilitates turnover of nonnative GRP94 marked by hyperglycosylation
The tight coupling of protein folding pathways with disposal mechanisms promotes the efficacy of protein production in the endoplasmic reticulum (ER). It has been hypothesized that the ER-resident molecular chaperone glucose-regulated protein 94 (GRP94) is part of this quality control coupling because it supports folding of select client proteins yet also robustly associates with the lectin ost...
IBiology: communicating the process of science
The Internet hosts an abundance of science video resources aimed at communicating scientific knowledge, including webinars, massive open online courses, and TED talks. Although these videos are efficient at disseminating information for diverse types of users, they often do not demonstrate the process of doing science, the excitement of scientific discovery, or how new scientific knowledge is d...
Modeling and Validating the Cost and Clinical Pathway of Colorectal Cancer
Cancer is a major cause of morbidity and mortality, and colorectal cancer (CRC) is the third most common cancer in the world. The estimated costs of CRC treatment vary considerably, and if CRC costs in a model are based on empirically estimated total costs of stage I, II, III, or IV treatments, then they lack some flexibility to capture future changes in CRC treatment. The purpose was 1) to des...