Porcine Enamel Protein Fractions Contain Transforming Growth Factor‐β1

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141064/1/jper1688.pd

Role of methionine adenosyltransferase 2A in bovine preimplantation development and its associated genomic regions

Methionine adenosyltransferase (MAT) is involved in folate-mediated one-carbon metabolism, which is essential for preimplantation embryos in terms of both short-term periconceptional development and long-term phenotypic programming beyond the periconceptional period. Here, our immunofluorescence analysis of bovine oocytes and preimplantation embryos revealed the consistent expression of MAT2A (the catalytic subunit of the ubiquitously expressed-type of MAT isozyme) during this period. Addition of the MAT2A inhibitor FIDAS to the culture media of bovine preimplantation embryos reduced their blastocyst development, revealing the particular importance of MAT2A in successful blastocyst development. Exploration of MAT2A-associated genomic regions in bovine blastocysts using chromatin immunoprecipitation and sequencing (ChIP-seq) identified candidate MAT2A-associated genes implicated not only in short-term periconceptional embryo development, but also in long-term phenotypic programming during this period in terms of growth, metabolism, and immune functions. These results suggest the critical involvement of MAT2A in the periconceptional period in life-long programming of health and disease as well as successful preimplantation development

Mutual Effects of Orexin and Bone Morphogenetic Proteins on Gonadotropin Expression by Mouse Gonadotrope Cells

Orexin plays a key role in the regulation of sleep and wakefulness and in feeding behavior in the central nervous system, but its receptors are expressed in various peripheral tissues including endocrine tissues. In the present study, we elucidated the effects of orexin on pituitary gonadotropin regulation by focusing on the functional involvement of bone morphogenetic proteins (BMPs) and clock genes using mouse gonadotrope L beta T2 cells that express orexin type 1 (OX1R) and type 2 (OX2R) receptors. Treatments with orexin A enhanced LH beta and FSH beta mRNA expression in a dose-dependent manner in the absence of GnRH, whereas orexin A in turn suppressed GnRH-induced gonadotropin expression in L beta T2 cells. Orexin A downregulated GnRH receptor expression, while GnRH enhanced OX1R and OX2R mRNA expression. Treatments with orexin A as well as GnRH increased the mRNA levels of Bmal1 and Clock, which are oscillational regulators for gonadotropin expression. Of note, treatments with BMP-6 and -15 enhanced OX1R and OX2R mRNA expression with upregulation of clock gene expression. On the other hand, orexin A enhanced BMP receptor signaling of Smad1/5/9 phosphorylation through upregulation of ALK-2/BMPRII among the BMP receptors expressed in L beta T2 cells. Collectively, the results indicate that orexin regulates gonadotropin expression via clock gene expression by mutually interacting with GnRH action and the pituitary BMP system in gonadotrope cells

Frequency-dependent ERK phosphorylation in spinal neurons by electric stimulation of the sciatic nerve and the role in electrophysiological activity

The phosphorylation of extracellular signal-regulated kinase (pERK) in DRG and dorsal horn neurons is induced by the C-fiber electrical stimulation to the peripheral nerve. The present study was designed to investigate the expression and modulation of pERK in the rat dorsal horn neurons produced by repetitive electrical stimulation, and its involvement in the electrophysiological activity of dorsal horn neurons. Electrical stimulation of C-fiber intensity at different frequencies was applied to the sciatic nerve; the stimuli-induced pERK expression and the activity in dorsal horn neurons were studied by immunohistochemistry and extracellular recording, respectively. Electrical stimulation of C-fibers (3 mA) induced pERK expression in dorsal horn neurons in a frequency-dependent manner, indicating that the frequency of electrical stimulation is an important factor which activates the intracellular signal pathway in the spinal cord. To demonstrate the underlying mechanism of this frequency-dependent pERK expression, an NMDA receptor antagonist, MK-801, and a voltage sensitive calcium channel antagonist, nifedipine, were administrated intrathecally before the stimulation. We found that high frequency (0.5 Hz and 10 Hz) but not low frequent (0.05 Hz) stimulus-evoked pERK was partially inhibited by MK-801. Both high and low frequency stimulus-evoked pERK were inhibited by the nifedipine treatment. The extracellular single unit activities were recorded from the laminae I-II and V of the L4-5 dorsal horn, and we found that blockage of the intracellular ERK signal suppressed the wind-up responses in a dose-dependent manner. In contrast, any change in the mechanically evoked responses was not observed following the administration of ERK inhibitor. These observations indicate that ERK activation plays an important role in the induction of the wind-up responses in dorsal horn nociceptive neurons

Higher Ambulatory Blood Pressure Is Associated With Aortic Valve Calcification in the Elderly: A Population-Based Study

Aortic valve calcification (AVC) without outflow obstruction (stenosis) is common in the elderly and increases the risk of cardiovascular morbidity and mortality. Although high blood pressure (BP) measured at the doctor’s office is known to be associated with AVC, little is known about the association between 24-hour ambulatory BP (ABP) and AVC. Our objective was to clarify the association between ABP variables and AVC. The study population consisted of 737 patients (mean age, 71±9 years) participating in the Cardiovascular Abnormalities and Brain Lesions study who underwent 24-hour ABP monitoring. Each aortic valve leaflet was graded on a scale of 0 (normal) to 3 (severe calcification). A total valve score (values 0–9) was calculated as the sum of all leaflet scores. Advanced AVC (score ≥4) was present in 77 subjects (10.4%). All of the systolic ABP variables (except systolic BP nocturnal decline) and mean asleep diastolic BP were positively associated with advanced calcification, whereas normal dipping status and diastolic BP nocturnal decline were negatively associated. Multiple regression analysis indicated that mean awake diastolic BP (odds ratio, 1.31 [95% CI, 1.01–1.71]) and asleep diastolic BP (odds ratio, 1.34 [95% CI, 1.04–1.72]) remained independently associated with advanced calcification after adjustment for age, sex, cigarette smoking, diabetes mellitus, hypercholesterolemia, hypertension, serum creatinine, and any degree of aortic insufficiency. Diastolic ABP is independently associated with advanced calcification. This finding may have important implications in gaining further insight into the mechanism of AVC

Usefulness of Cardiac Computed Tomography in the Diagnosis of Prosthetic Coronary Artery Graft with Interposition Procedure

An 80-year-old Japanese man was admitted with orthopnea and pitting edema of both lower legs. We diagnosed congestive heart failure (CHF) on the basis of a chest X-ray and an echocardiogram. An electrocardiogram showed a heart rate of 120 beats/min with atrial fibrillation rhythm (Af). The patient developed aortic valve failure and destruction of the base of right coronary artery (RCA) due to infectious endocarditis at 71 years of age. The patient underwent aortic valve replacement and coronary artery bypass grafting with an interposed graft with polyester vascular graft to RCA. The patient recovered from CHF after the 6 days of treatment with diuretics and verapamil. We confirmed the patency of coronary arteries and bypass grafts using a 64-slice cardiac computed tomography scan (CT) and diagnosed CHF due to Af. Here we describe the estimation of the prosthetic coronary artery graft patency with the interposition procedure using 64-slice cardiac CT