Thyroid hormone receptor regulates most genes independently of fibroblast growth factor 21 in liver

Thyroid hormone (TH) acts through specific receptors (TRs), which are conditional transcription factors, to induce fibroblast growth factor 21 (FGF21), a peptide hormone that is usually induced by fasting and that influences lipid and carbohydrate metabolism via local hepatic and systemic endocrine effects. While TH and FGF21 display overlapping actions when administered, including reductions in serum lipids, according to the current models these hormones act independently in vivo. In this study, we examined mechanisms of regulation of FGF21 expression by TH and tested the possibility that FGF21 is required for induction of hepatic TH-responsive genes. We confirm that active TH (triiodothyronine (T3)) and the TRβ-selective thyromimetic GC1 increase FGF21 transcript and peptide levels inmouse liver and that this effect requires TRβ. T3 also induces FGF21 in cultured hepatocytes and this effect involves direct actions of TRβ1, which binds a TRE within intron 2 of FGF21. Gene expression profiles of WT and Fgf21-knockout mice are very similar, indicating that FGF21 is dispensable for the majority of hepatic T3 gene responses. A small subset of genes displays diminished T3 response in the absence of FGF21. However, most of these are not obviously directly involved in T3-dependent hepatic metabolic processes. Consistent with these results, T3-dependent effects on serum cholesterol are maintained in the Fgf21-/- background and we observe no effect of the Fgf21-knockout background on serum triglycerides and glucose. Our findings indicate that T3 regulates the genes involved in classical hepatic metabolic responses independently of FGF21

Silicon carbide particulates incorporated into microalloyed steel surface using TIG: microstructure and properties

Surface metal matrix composites have been developed to enhance properties such as erosion, wear and corrosion of alloys. In this study, ~5 µm or ~75 µm SiC particulates were preplaced on a microalloyed steel. Single track surface zones were melted by a tungsten inert gas torch, and the effect of two heat inputs, 420Jmm-1 and 840 Jmm-1,compared. The results showed that the samples melted using 420Jmm-1 were crack-free. Pin-on-disk wear testing under dry sliding conditions were conducted. The effects of load and sliding velocity were used to characterise the performance of the crack-free samples. Microstructural and X-ray diffraction studies of the surface showed that the SiC had dissolved, and that martensite, was the main phase influencing the hardness

Epidemiologic Study of Malassezia Yeasts in Acne Patients by Analysis of 26S rDNA PCR-RFLP

Background: Although acne is a common follicular inflammatory dermatosis, studies of the relationship between Malassezia yeasts and acne have rarely been conducted. Objective: We sought to identify Malassezia yeasts from acne patients and establish a relationship between specific types of species of Malassezia and acne. Methods: Sixty acne patients were enrolled. Each strain obtained was identified as one of eleven species by 26S rDNA PCR-RFLP. We then compared these data with those of age- and sex-matched healthy subjects. Results: Growth of Malassezia was evident in fewer patients with acne (50%) in comparison to controls (70.6%). M. restricta was dominant in patients with acne (23.9%), whereas M. globosa was most common (26.7%) in healthy controls. In the patients group, the rate was the highest (71.7%) in the twenties and, in terms of body site, the rate was the highest (60%) in the chest. In the control group, the rate was the highest (75.0%) in the thirties and in the forehead (85.0%). Conclusion: The detection rate of Malassezia yeasts was conspicuously low in the acne patients group. Statistically significant differences were observed between the patient and the control groups in the twenties and thirties, and in terms of body site, in th

Increased Circulating Endothelial Microparticles and Carotid Atherosclerosis in Obstructive Sleep Apnea

Background and Purpose Endothelial impairment is a linking mechanism between obstructive sleep apnea (USA) and cardiovascular diseases Profiles of endothelial micropanicles (EMPs) and endothelial progenitor cells (EPCs) reflect the degree of endothelial impairment The aims of this study were to measure the levels of EMI`s and progenitor cells in USA, determine the correlations between these factors and USA severity and the deuce of atherosclerosis, and document any changes in these factors after therapy Methods Subjects with (n=82) and without (n=22) OSA were recruited prospectively We measured the number of colony-forming units (CM) in cell cultuie as the endothelial progenitor cell index, and the number of EMPs using flow cytometry with CD31 [platelet endothelial cell adhesion molecule (PECAM)], CD42 (platelet glycoprotem), annexm V, and CD62E (E-selectin) antibodies at baseline and Act 4-6 weeks of continuous positive airway pressure (CPA P) therapy Carotid int ima-media thickness (IMT) was regarded as a marker of atherosclerosis Results The levels of PECAM(+)CD42(-) (p<0 001). PECAM(+)annexin V(+) (p<0 001), and E-selectin(+) micropamcles (p=0 001) were higher in USA subjects than in non-USA subjects The number of CRJ did not differ between the two groups OSA severity independently predicted the levels of PECAM(+)CD42(-) (p=0 02) and PECA(+)annexin V(+) (p=0 004) Carotid IMT was correlated with USA severity (p<0 001), PECAM(+)CD42: (p=0 03), and PECAM(+)annexin (p=0 01) Neither USA severity nor carotid IMT was correlated with either the number of CFI) or E-selectin(+) CPAP therapy decreased the occurrence of E-selecte (p<0 001) in 21 of the USA subjects, but had no effect on the other micioparticles of the number CFU Conclusions USA led to the overproduction of EMI`s, which moderately correlated with USA seventy and the degree of atherosclerosis, and partly responded to therapy The endothelial impairment might contribute to future cardiovascular events J Clin Neurol 2010;6`89-98This research was supported by the Stem Cell Research Center of the 21st Century Frontier Research Program funded by the Ministry of Science and Technology, Republic of Korea (#SC4120).de Lima AMJ, 2010, RESPIRATION, V79, P370, DOI 10.1159/000227800Jung KH, 2009, ANN NEUROL, V66, P191, DOI 10.1002/ana.21681Ayers L, 2009, EUR RESPIR J, V33, P574, DOI 10.1183/09031936.00107408Akinnusi ME, 2009, AM J RESP CRIT CARE, V179, P328Christou K, 2009, SLEEP MED, V10, P87, DOI 10.1016/j.sleep.2007.10.011Barcelo A, 2008, THORAX, V63, P946, DOI 10.1136/thx.2007.093740Dorkova Z, 2008, CHEST, V134, P686, DOI 10.1378/chest.08-0556Robinson GV, 2008, THORAX, V63, P855, DOI 10.1136/thx.2007.088096Somers VK, 2008, CIRCULATION, V118, P1080, DOI 10.1161/CIRCULATIONAHA.107.189375Hirschi KK, 2008, ARTERIOSCL THROM VAS, V28, P1584, DOI 10.1161/ATVBAHA.107.155960Daniel L, 2008, NEPHROL DIAL TRANSPL, V23, P2129, DOI 10.1093/ndt/gfn029Martin K, 2008, LUNG, V186, P145, DOI 10.1007/s00408-008-9073-yAmabile N, 2008, AM J RESP CRIT CARE, V177, P1268, DOI 10.1164/rccm.200710-1458OCHeiss C, 2008, J AM COLL CARDIOL, V51, P1760, DOI 10.1016/j.jacc.2008.01.040Chu K, 2008, STROKE, V39, P1441, DOI 10.1161/STROKEAHA.107.499236Jelic S, 2008, CIRCULATION, V117, P2270, DOI 10.1161/CIRCULATIONAHA.107.741512Lee ST, 2008, NEUROLOGY, V70, P1510Bakouboula B, 2008, AM J RESP CRIT CARE, V177, P536, DOI 10.1164/rccm.200706-840OCLopez-Jimenez F, 2008, CHEST, V133, P793, DOI 10.1378/chest.07-0800de la Pena M, 2008, RESPIRATION, V76, P28, DOI 10.1159/000109643WON CHJ, 2008, P AM THORAC SOC, V5, P193Kloner RA, 2007, CIRCULATION, V116, P1306, DOI 10.1161/CIRCULATIONAHA.106.678375El Solh AA, 2007, AM J RESP CRIT CARE, V175, P1186, DOI 10.1164/rccm.200611-1598OCIBER C, 2007, AASM MANUAL SCORINGMONTSERRAT JM, 2007, AM J RESP CRIT CARE, V176, P6Pirro M, 2006, ARTERIOSCL THROM VAS, V26, P2530, DOI 10.1161/01.ATV.0000243941.72375.15Ryan S, 2006, AM J RESP CRIT CARE, V174, P824, DOI 10.1164/rccm.200601-066OCBoulanger CM, 2006, HYPERTENSION, V48, P180, DOI 10.1161/01.HYP.0000231507.00962.b5Arteaga RB, 2006, AM J CARDIOL, V98, P70, DOI 10.1016/j.amjcard.2006.01.054Robinson GV, 2006, EUR RESPIR J, V27, P1229, DOI 10.1183/09031936.06.00062805Werner N, 2005, NEW ENGL J MED, V353, P999Mezentsev A, 2005, AM J PHYSIOL-HEART C, V289, pH1106, DOI 10.1152/ajpheart.00265.2005Minoguchi K, 2005, AM J RESP CRIT CARE, V172, P625, DOI 10.1164/rccm.200412-1652OCMassa M, 2005, BLOOD, V105, P199, DOI 10.1182/blood-2004-05-1831Kim J, 2004, AM J RESP CRIT CARE, V170, P1108, DOI 10.1164/rccm.200404-519OCJy W, 2004, J THROMB HAEMOST, V2, P1842Tramontano AF, 2004, BIOCHEM BIOPH RES CO, V320, P34, DOI 10.1016/j.bbrc.2004.05.127Ip MSM, 2004, AM J RESP CRIT CARE, V169, P348, DOI 10.1164/rccm.200306.767OCBarba C, 2004, LANCET, V363, P157Bernal-Mizrachi L, 2003, AM HEART J, V145, P962, DOI 10.1016/S0002-8703(03)00103-0Jimenez JJ, 2003, THROMB RES, V109, P175, DOI 10.1016/S0049-3848(03)00064-1Hill JM, 2003, NEW ENGL J MED, V348, P593Preston RA, 2003, HYPERTENSION, V41, P211, DOI 10.1161/01.HYP.0000049760.15764.2DSabatier F, 2002, DIABETES, V51, P2840, DOI 10.2337/diabetes.51.9.2840El-Solh AA, 2002, CHEST, V121, P1541Boulanger CM, 2001, CIRCULATION, V104, P2649Barbe F, 2001, ANN INTERN MED, V134, P1015Chin K, 2000, AM J MED, V109, P562Lusis AJ, 2000, NATURE, V407, P233Ohga E, 1999, J APPL PHYSIOL, V87, P10YOUNG T, 1993, NEW ENGL J MED, V328, P1230JOHNS MW, 1991, SLEEP, V14, P540

Defining the Conformational Features of Anchorless, Poorly Neuroinvasive Prions

Infectious prions cause diverse clinical signs and form an extraordinary range of structures, from amorphous aggregates to fibrils. How the conformation of a prion dictates the disease phenotype remains unclear. Mice expressing GPI-anchorless or GPI-anchored prion protein exposed to the same infectious prion develop fibrillar or nonfibrillar aggregates, respectively, and show a striking divergence in the disease pathogenesis. To better understand how a prion's physical properties govern the pathogenesis, infectious anchorless prions were passaged in mice expressing anchorless prion protein and the resulting prions were biochemically characterized. Serial passage of anchorless prions led to a significant decrease in the incubation period to terminal disease and altered the biochemical properties, consistent with a transmission barrier effect. After an intraperitoneal exposure, anchorless prions were only weakly neuroinvasive, as prion plaques rarely occurred in the brain yet were abundant in extracerebral sites such as heart and adipose tissue. Anchorless prions consistently showed very high stability in chaotropes or when heated in SDS, and were highly resistant to enzyme digestion. Consistent with the results in mice, anchorless prions from a human patient were also highly stable in chaotropes. These findings reveal that anchorless prions consist of fibrillar and highly stable conformers. The additional finding from our group and others that both anchorless and anchored prion fibrils are poorly neuroinvasive strengthens the hypothesis that a fibrillar prion structure impedes efficient CNS invasion

Blood Feeding and Insulin-like Peptide 3 Stimulate Proliferation of Hemocytes in the Mosquito Aedes aegypti

All vector mosquito species must feed on the blood of a vertebrate host to produce eggs. Multiple cycles of blood feeding also promote frequent contacts with hosts, which enhance the risk of exposure to infectious agents and disease transmission. Blood feeding triggers the release of insulin-like peptides (ILPs) from the brain of the mosquito Aedes aegypti, which regulate blood meal digestion and egg formation. In turn, hemocytes serve as the most important constitutive defense in mosquitoes against pathogens that enter the hemocoel. Prior studies indicated that blood feeding stimulates hemocytes to increase in abundance, but how this increase in abundance is regulated is unknown. Here, we determined that phagocytic granulocytes and oenocytoids express the A. aegypti insulin receptor (AaMIR). We then showed that: 1) decapitation of mosquitoes after blood feeding inhibited hemocyte proliferation, 2) a single dose of insulin-like peptide 3 (ILP3) sufficient to stimulate egg production rescued proliferation, and 3) knockdown of the AaMIR inhibited ILP3 rescue activity. Infection studies indicated that increased hemocyte abundance enhanced clearance of the bacterium Escherichia coli at lower levels of infection. Surprisingly, however, non-blood fed females better survived intermediate and high levels of E. coli infection than blood fed females. Taken together, our results reveal a previously unrecognized role for the insulin signaling pathway in regulating hemocyte proliferation. Our results also indicate that blood feeding enhances resistance to E. coli at lower levels of infection but reduces tolerance at higher levels of infection

Biochemical Properties of Highly Neuroinvasive Prion Strains

Infectious prions propagate from peripheral entry sites into the central nervous system (CNS), where they cause progressive neurodegeneration that ultimately leads to death. Yet the pathogenesis of prion disease can vary dramatically depending on the strain, or conformational variant of the aberrantly folded and aggregated protein, PrPSc. Although most prion strains invade the CNS, some prion strains cannot gain entry and do not cause clinical signs of disease. The conformational basis for this remarkable variation in the pathogenesis among strains is unclear. Using mouse-adapted prion strains, here we show that highly neuroinvasive prion strains primarily form diffuse aggregates in brain and are noncongophilic, conformationally unstable in denaturing conditions, and lead to rapidly lethal disease. These neuroinvasive strains efficiently generate PrPSc over short incubation periods. In contrast, the weakly neuroinvasive prion strains form large fibrillary plaques and are stable, congophilic, and inefficiently generate PrPSc over long incubation periods. Overall, these results indicate that the most neuroinvasive prion strains are also the least stable, and support the concept that the efficient replication and unstable nature of the most rapidly converting prions may be a feature linked to their efficient spread into the CNS