RSSEffects of Cord Serum Insulin, IGF-II, IGFBP-2, IL-6 and Cortisol Concentrations on Human Birth Weight and Length: Pilot Study.
Source
Department of Paediatrics, University Hospital of Parma, Parma, Italy.
Abstract
BACKGROUND:
The IGF system is recognised to be important for fetal growth. We previously described increased Insulin-like growth factor binding protein (IGFBP)-2 cord serum concentrations in intra-uterine growth retardation (IUGR) compared with appropriate for gestational age (AGA) newborns, and a positive relationship of IGFBP-2 with Interleukin (IL)-6. The role of cortisol in the fetus at birth is largely unknown, and interactions among peptides are their real effect on birth size is unknown. Furthermore, almost all studies have previously assayed peptides in serum several years after birth, and follow-up data from pregnancy are always lacking. This study aimed at establishing and clarifying the effect of cord serum insulin, IGF-II, IGFBP-2, cortisol and IL-6 concentrations on birth length and weight.
METHODS:
23 IUGR and 37 AGA subjects were followed up from the beginning of pregnancy, and were of comparable gestational age. Insulin, IGF-II, IGFBP-2, cortisol and IL-6 concentrations were assayed in cord serum at birth, and a multiple regression model was designed and applied to assess which were the significant biochemical determinants of birth size.
RESULTS:
Insulin, cortisol, and IL-6, showed similar concentrations in IUGR and AGA as previously described, whereas IGF-II was lower, and IGFBP-2 increased in IUGR compared with AGA. IGF-II serum concentration was found to have a significant positive effect on both birth length (r:(:)0.546; p: 0.001) and weight (r:0.679; p: 0.0001). IGFBP-2 had a near significant negative effect on both birth weight (r:-0.342; p: 0.05) and length (r:-0.372; p:0.03).
CONCLUSION:
IGF-II cord serum concentration was shown to have a significant positive effect on both birth length and weight, whereas IGFBP-2 had a significant negative effect. Insulin, cortisol, and IL-6 cord serum concentrations had no significant effect on birth size.
- PMID:
- 22242132
- [PubMed - in process]
Interleukin 15 levels in serum may predict a severe disease course in patients with early arthritis.
Source
Rheumatology Service, Hospital Universitario de La Princesa, IIS Princesa, Madrid, Spain.
Abstract
BACKGROUND:
Interleukin-15 (IL-15) is thought to be involved in the physiopathological mechanisms of RA and it can be detected in the serum and the synovial fluid of inflamed joints in patients with RA but not in patients with osteoarthritis or other inflammatory joint diseases. Therefore, the objective of this work is to analyse whether serum IL-15 (sIL-15) levels serve as a biomarker of disease severity in patients with early arthritis (EA).
METHODOLOGY AND RESULTS:
Data from 190 patients in an EA register were analysed (77.2% female; median age 53 years; 6-month median disease duration at entry). Clinical and treatment information was recorded systematically, especially the prescription of disease modifying anti-rheumatic drugs. Two multivariate longitudinal analyses were performed with different dependent variables: 1) DAS28 and 2) a variable reflecting intensive treatment. Both included sIL-15 as predictive variable and other variables associated with disease severity, including rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (ACPA). Of the 171 patients (638 visits analysed) completing the follow-up, 71% suffered rheumatoid arthritis and 29% were considered as undifferentiated arthritis. Elevated sIL-15 was detected in 29% of this population and this biomarker did not overlap extensively with RF or ACPA. High sIL-15 levels (β Coefficient [95% confidence interval]: 0.12 [0.06-0.18]; p<0.001) or ACPA (0.34 [0.01-0.67]; p = 0.044) were significantly and independently associated with a higher DAS28 during follow-up, after adjusting for confounding variables such as gender, age and treatment. In addition, those patients with elevated sIL-15 had a significantly higher risk of receiving intensive treatment (RR 1.78, 95% confidence interval 1.18-2.7; p = 0.007).
CONCLUSIONS:
Patients with EA displaying high baseline sIL-15 suffered a more severe disease and received more intensive treatment. Thus, sIL-15 may be a biomarker for patients that are candidates for early and more intensive treatment.
- PMID:
- 22242124
- [PubMed - in process]
The Cysteine Rich Necrotrophic Effector SnTox1 Produced by Stagonospora nodorum Triggers Susceptibility of Wheat Lines Harboring Snn1.
Source
Department of Plant Pathology, North Dakota State University, Fargo, North Dakota, United States of America.
Abstract
The wheat pathogen Stagonospora nodorum produces multiple necrotrophic effectors (also called host-selective toxins) that promote disease by interacting with corresponding host sensitivity gene products. SnTox1 was the first necrotrophic effector identified in S. nodorum, and was shown to induce necrosis on wheat lines carrying Snn1. Here, we report the molecular cloning and validation of SnTox1 as well as the preliminary characterization of the mechanism underlying the SnTox1-Snn1 interaction which leads to susceptibility. SnTox1 was identified using bioinformatics tools and verified by heterologous expression in Pichia pastoris. SnTox1 encodes a 117 amino acid protein with the first 17 amino acids predicted as a signal peptide, and strikingly, the mature protein contains 16 cysteine residues, a common feature for some avirulence effectors. The transformation of SnTox1 into an avirulent S. nodorum isolate was sufficient to make the strain pathogenic. Additionally, the deletion of SnTox1 in virulent isolates rendered the SnTox1 mutated strains avirulent on the Snn1 differential wheat line. SnTox1 was present in 85% of a global collection of S. nodorum isolates. We identified a total of 11 protein isoforms and found evidence for strong diversifying selection operating on SnTox1. The SnTox1-Snn1 interaction results in an oxidative burst, DNA laddering, and pathogenesis related (PR) gene expression, all hallmarks of a defense response. In the absence of light, the development of SnTox1-induced necrosis and disease symptoms were completely blocked. By comparing the infection processes of a GFP-tagged avirulent isolate and the same isolate transformed with SnTox1, we conclude that SnTox1 may play a critical role during fungal penetration. This research further demonstrates that necrotrophic fungal pathogens utilize small effector proteins to exploit plant resistance pathways for their colonization, which provides important insights into the molecular basis of the wheat-S. nodorum interaction, an emerging model for necrotrophic pathosystems.
- PMID:
- 22241993
- [PubMed - in process]
Glycoproteomic characterisation of recombinant mouse alpha-dystroglycan.
Source
Centre for Genetics and Genomics, School of Biology, Queen's Medical Centre, University of Nottingham, Nottingham, NG7 2UH, UK D.Mekhaiel@liverpool.ac.uk.
Abstract
α-Dystroglycan is a key component of the dystrophin-glycoprotein complex. Aberrant glycosylation of the protein has been linked to various forms of congenital muscular dystrophy. Unusually α-dystroglycan has previously been demonstrated to be modified with both O-GalNAc and O-mannose initiated glycans. In the present study, Fc-tagged recombinant mouse α-dystroglycan was expressed and purified from HEK293T cells. α-Dystroglycan glycopeptides were characterized by glycoproteomic strategies using both Nano-liquid chromatography MALDI- and Electrospray tandem mass spectrometry. A total of 14 different peptide sequences and 38 glycopeptides were identified which displayed heterogeneous O-glycosylation. These data provide new insights into the complex domain specific O-glycosylation of α-dystroglycan.
- PMID:
- 22241827
- [PubMed - as supplied by publisher]
The lipid linked oligosaccharide donor specificities of Trypanosoma brucei oligosaccharyltransferases.
Source
Division of Biological Chemistry and Drug Discovery, The College of Life Sciences, University of Dundee, Dundee, UK.
Abstract
We recently presented a model for site-specific protein N-glycosylation in Trypanosoma brucei whereby the TbSTT3A oligosaccharyltransferase first selectively transfers biantennary Man(5)GlcNAc(2) from the lipid linked oligosaccharide donor Man(5)GlcNAc(2)-PP-Dol to N-glycosylation sequons in acidic to neutral peptide sequences and TbSTT3B selectively transfers triantennary Man(9)GlcNAc(2) to any remaining sequons. In this paper, we investigate the specificities of the two oligosaccharyltransferases for their preferred lipid linked oligosaccharide donors by glycotyping the variant surface glycoprotein synthesized by bloodstream form T.brucei TbALG12 null mutants. The TbALG12 gene encodes the α1-6 mannosyltransferase that converts Man(7)GlcNAc(2)-PP-Dol to Man(8)GlcNAc(2)-PP-Dol. The variant surface glycoprotein synthesized by the TbALG12 null mutant in the presence and absence of α-mannosidase inhibitors was characterized by electrospray mass spectrometry both intact and as Pronase glycopetides. The results show that TbSTT3A is able to transfer Man(7)GlcNAc(2) as well as Man(5)GlcNAc(2) to its preferred acidic glycosylation site at Asn263 and that, in the absence of Man(9)GlcNAc(2)-PP-Dol, TbSTT3B transfers both Man(7)GlcNAc(2) and Man(5)GlcNAc(2) to the remaining site at Asn428, albeit with low efficiency. These data suggests that the preferences of TbSTT3A and TbSTT3B for their lipid linked oligosaccharide donors are based on the c-branch of the Man(9)GlcNAc(2) oligosaccharide, such that the presence of the c-branch prevents recognition and/or transfer by TbSTT3A, whereas the presence of the c-branch enhances recognition and/or transfer by TbSTT3B.
- PMID:
- 22241825
- [PubMed - as supplied by publisher]
Direct interaction of ligand-receptor pairs specifying stomatal patterning.
Source
Department of Biology.
Abstract
Valves on the plant epidermis called stomata develop according to positional cues, which likely involve putative ligands (EPIDERMAL PATTERNING FACTORS [EPFs]) and putative receptors (ERECTA family receptor kinases and TOO MANY MOUTHS [TMM]) in Arabidopsis. Here we report the direct, robust, and saturable binding of bioactive EPFpeptides to the ERECTA family. In contrast, TMM exhibits negligible binding to EPF1 but binding to EPF2. The ERECTA family forms receptor homomers in vivo. On the other hand, TMM associates with the ERECTA family but not with itself. While ERECTA family receptor kinases exhibit complex redundancy, blocking ERECTA and ERECTA-LIKE1 (ERL1) signaling confers specific insensitivity to EPF2 and EPF1, respectively. Our results place the ERECTA family as the primary receptors for EPFs with TMM as a signal modulator and establish EPF2-ERECTA and EPF1-ERL1 as ligand-receptor pairs specifying two steps of stomatal development: initiation and spacing divisions.
- PMID:
- 22241782
- [PubMed - as supplied by publisher]
Regulation of iron metabolism in Hamp (-/-) mice in response to iron-deficient diet.
Source
Diabetes and Nutritional Sciences Division, School of Medicine, King's College London, 150 Stamford Street, London, SE1 9NH, UK.
Abstract
BACKGROUND:
Hepcidin, the liver-secreted iron regulatory peptide, maintains systemic iron homeostasis in response to several stimuli including dietary iron levels and body iron status. In addition, iron metabolism is controlled by several local regulatory mechanisms including IRP and Hif-2α activities independently of hepcidin. However, the roles of these mechanisms and their interaction particularly in hepcidin-deficient individuals are not yet fully understood. We, therefore, aimed to explore whether Hamp disruption affects iron homeostatic responses to dietary iron deficiency.
METHODS:
Hepcidin1 knockout (Hamp (-/-)) mice and heterozygous littermates were fed with control or iron-deficient diet for 2 weeks. The expression of iron-related genes and proteins were determined by quantitative PCR and Western blot, respectively.
RESULTS:
Two-week iron-deficient diet feeding in Hamp (-/-) mice did not alter serum iron but significantly reduced liver non-heme iron levels. This was also associated with increased ferroportin protein expression in the duodenum and spleen, whereas decreased expression was found in the liver. In addition, significant inductive effects of iron-deficient diet on Dcytb and DMT1 mRNA expression in the duodenum were noted with more pronounced effects in Hamp (-/-) mice compared with controls.
CONCLUSIONS:
Hamp (-/-) mice exhibited a more dramatic increase in the expression of iron transport machinery, which may be responsible for the unaltered serum iron levels upon iron-deficient diet feeding in these mice. Despite the lack of hepcidin, Hamp (-/-) mice can maintain a degree of iron homeostasis in response to altered dietary iron through several hepcidin-independent mechanisms.
- PMID:
- 22241739
- [PubMed - as supplied by publisher]
β-Amyloid peptide is internalized into chick retinal neurons and alters the distribution of myosin Vb.
Source
Instituto de Bioquímica Médica - Universidade Federal do Rio de Janeiro; Departamento de Biociências da Atividade Física - Escola da Educação Física e Desportos - Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, 21941-902, Brazil.
Abstract
The most common neurodegenerative disorder afflicting the aging human population is Alzheimer's disease. A major hallmark of Alzheimer's disease is dementia from a loss of neuronal function, attributed to the presence and accumulation of β-amyloid peptide into senile plaques. Preceding senile plaque formation, abnormalities in axons can be observed as changes in morphologies and intracellular trafficking. Recently, it has been recognized that β-amyloid also accumulates within neurons and this intraneuronal β-amyloid accumulation has been reported to be critical in the disruption of synapses and cognitive function. Here we report on the internalization of a fluorescently labeled β-amyloidpeptide into cultured chick retinal neurons. The pattern of β-amyloid distribution during the time course of incubation is reminiscent of the endocytic pathway. Furthermore, the distribution of the internalized β-amyloid peptide converges with that of myosin Vb and both relocalize from the axon to cell body. These observations are consistent with the hypothesis that Alzheimer's disease proceeds as a result of an imbalance between β-amyloid production and β-amyloid clearance, suggesting a role for myosin Vb in this process. © 2012 Wiley Periodicals, Inc.
Copyright © 2012 Wiley Periodicals, Inc.
- PMID:
- 22241730
- [PubMed - as supplied by publisher]
Human Protein Arginine Methyltransferase 7 (PRMT7) is a Type III Enzyme Forming ω-NG-Monomethylated Arginine Residues.
Source
UCLA, United States.
Abstract
Full-length human protein arginine methyltransferase 7 (PRMT7) expressed as a fusion protein in Escherichia coli was initially found to generate only ω-N(G) monomethylated arginine residues in small peptides, suggesting that it is a type III enzyme. A later study, however, characterized fusion proteins of PRMT7 expressed in bacterial and mammalian cells as a type II/type I enzyme, capable of producing symmetrically dimethylated arginine (type II activity) as well as small amounts of asymmetric dimethylarginine (type I activity). We have sought to clarify the enzymatic activity of human PRMT7. We analyzed the in vitro methylation products of a glutathione-S-transferase (GST)-PRMT7 fusion protein with robust activity using a variety of arginine-containing synthetic peptides and protein substrates, including a GST-fusion with the N-terminal domain of fibrillarin (GST-GAR), myelin basic protein and recombinant human histones H2A, H2B, H3, and H4. Regardless of methylation reaction conditions (incubation time, reaction volume and substrate concentration), we found that PRMT7 only produces ω-N(G)-monomethylarginine with these substrates. In control experiments, we showed that mammalian GST-PRMT1 and Myc-PRMT5 were, unlike PRMT7, able to dimethylate bothpeptide P-SmD3 and SmB/D3 to give the expected asymmetric and symmetric products, respectively. These experiments show that PRMT7 is indeed a type III human methyltransferase capable of forming only ω-N(G)-monomethylarginine, not ADMA or SDMA, under the conditions tested.
- PMID:
- 22241471
- [PubMed - as supplied by publisher]
A functional variant of the collagen type III alpha1 gene modify risk of sporadic intracranial aneurysms.
Source
Sino-German Laboratory for Molecular Medicine, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishilu, Beijing, 100037, People's Republic of China.
Abstract
Abnormalities in type III collagen in the arterial walls cause certain familial intracranial aneurysms (IAs); however, it remains unknown whether COL3A1 variants contribute to the risk of sporadic IAs. To study whether COL3A1 variants are associated with sporadic IAs, the association of COL3A1 variants with sporadic IAs was tested in 298 cases and 488 controls, replicated in an independent population of 192 cases and 1,690 controls, and further verified in 633 patients with intra-cerebral hemorrhage, 1,074 hypertensives, and 1,883 controls. We found that allele A of SNP rs1800255 conferred a 1.71-fold increased risk for IAs (adjusted odds ratio: OR = 1.71, 95% confidence interval: CI 1.19-2.45, P = 0.004) and results in an amino acid change of Ala698Thr, which led to a lower thermal stability of the peptide. These results were confirmed in the independent study. The associations were independent of the presence of hemorrhagic stroke and hypertension. These results support the view that the functional variant of COL3A1 is genetic risk factors for IAs in the Chinese population.
- PMID:
- 22241462
- [PubMed - as supplied by publisher]
Cell-penetrating properties of the transactivator of transcription and polyarginine (R9) peptides, their conjugative effect on nanoparticles and the prospect of conjugation with arsenic trioxide.
Source
aNanomedicine-Laboratory of Immunology and Molecular Biomedical Research (LIMBR), Centre for Biotechnology and Interdisciplinary Biosciences (BioDeakin), Institute for Technology and Research Innovation (ITRI), Geelong Technology Precinct (GTP), Deakin University, Geelong, Vic., Australia bNano-biotech Lab, Department of Zoology, K.M. College, University of Delhi, Delhi, India.
Abstract
Cell-penetrating peptides (CPPs) are short chains of amino acids with the distinct ability to cross cell plasma membranes. They are usually between seven and 30 residues in length. The mechanism of action is still a highly debated subject among researchers; it seems that a commonality between all CPPs is the presence of positively charged residues within the amino acid chain. Polyarginine and the transactivator of transcription peptide are two widely used CPPs. One distinct application of these CPPs is the ability to further enhance the therapeutic properties of a range of different agents. One group of agents of particular importance are nanoparticles (NPs). Most NPs have no mechanism for cellular uptake. Hence, by conjugating CPPs to NPs, the amount of NPs taken up by cells can be increased, and therefore, the therapeutic benefits can be maximized. Some examples of this will be explored further in this review. In addition to CPPs, the concept of conjugation with the anticancer drug arsenic trioxide is reviewed and the prospect of transactivator of transcription-conjugated arsenic trioxide albumin microspheres is also discussed. Recent locked nucleic acid technology to stabilize nucleotides (RNA or DNA) aptamer complexes able to target cancer cells more specifically and selectively to kill tumour cells and spare normal body cells. NPs tagged with modified locked nucleic acid-aptamers have the potential to kill cancer cells more specifically and effectively while sparing normal cells.
- PMID:
- 22241171
- [PubMed - as supplied by publisher]
A fluorescent amino acid probe to monitor efficiency of peptide conjugation to glass surfaces for high density microarrays.
Source
Department of Bioengineering and Center for Bioengineering Research, Bourns College of Engineering, University of California at Riverside, 900 University Avenue, Riverside, CA 92521, USA. jiayu.liao@ucr.edu.
Abstract
Using a fluorescent NBD amino acid, new protease substrates were developed that are attractive because of the excellent chemical stability and long wavelength of excitation (480 nm) of the NBD fluorophore. The fluorescent peptidesare synthesized by Fmoc solid-phase peptide synthesis. An example peptide was efficiently immobilized onto a microarray surface using click chemistry, and its proteolysis was monitored by fluorescence imaging. Excellent site specificity was achieved for the protease. Fluorescent peptides are also used to monitor the conjugation efficiency onto a surface using a standard microarray scanner.
- PMID:
- 22241083
- [PubMed - as supplied by publisher]
Insulin-like growth factor 1: common mediator of multiple enterotrophic hormones and growth factors.
Source
Department of Cell & Molecular Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Abstract
PURPOSE OF REVIEW:
To summarize the recent evidence that insulin-like growth factor 1 (IGF1) mediates growth effects of multiple trophic factors and discuss clinical relevance.
RECENT FINDINGS:
Recent reviews and original reports indicate benefits of growth hormone (GH) and long-acting glucagon-like peptide 2 (GLP2) analogs in short bowel syndrome and Crohn's disease. This review highlights the evidence that biomarkers of sustained small intestinal growth or mucosal healing and evaluation of intestinal epithelial stem cell biomarkers may improve clinical measures of intestinal growth or response to trophic hormones. Compelling evidence that IGF1 mediates growth effects of GH and GLP2 on intestine or linear growth in preclinical models of resection or Crohn's disease is presented, along with a concept that these hormones or IGF1 may enhance sustained growth if given early after bowel resection. Evidence that suppressor of cytokine signaling protein induction by GH or GLP2 in normal or inflamed intestine may limit IGF1-induced growth, but protect against risk of dysplasia or fibrosis, is reviewed. Whether IGF1 receptor mediates IGF1 action and potential roles of insulin receptors are addressed.
SUMMARY:
IGF1 has a central role in mediating trophic hormone action in small intestine. Better understanding of benefits and risks of IGF1, receptors that mediate IGF1 action, and factors that limit undesirable growth are needed.
- PMID:
- 22241077
- [PubMed - as supplied by publisher]
Innate immunity in the small intestine.
Source
Division of Gastroenterology, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA.
Abstract
PURPOSE OF REVIEW:
This article reviews the most recent publications on innate immunity in the small intestine. We will go over the innate immune receptors that act as sensors of microbial presence or cell injury, Paneth cells as the main epithelial cell type that secrete antimicrobial peptides, and mucosal production of immunoglobulin A (IgA). In addition, we will give an update on examples of imbalance of the innate immune response resulting in clinical disease with the most relevant example being Crohn's disease.
RECENT FINDINGS:
Toll-like receptors (TLRs) are involved in B-cell homing to the intestine, rejection of small intestinal allografts, and recruitment of mast cells. The TLR adaptor Toll/interleukin-1 receptor domain-containing adapter-inducing interferon-β is necessary to activate innate immunity after Yersinia enterocolitica infection. Moreover, MyD88 is required to keep the intestinal microbiota under control and physically separated from the epithelium, and RegIIIγ is responsible for the bacterial segregation from the lining epithelial cells. In Crohn's disease, ATG16L1 T300A variant promotes a proinflammatory response; and miR-196 downregulates a protective immunity-related GTPase family M protein (IRGM) polymorphism leading to impaired clearance of adherent Escherichia coli in the intestine.
SUMMARY:
The intestine is continuously exposed to dietary and microbial antigens. The host has to maintain intestinal homeostasis to keep the commensal and pathogenic bacteria under control. Some of the mechanisms to do so are by expression of innate immune receptors, production of antimicrobial peptides, secretion of IgA, or autophagy of intracellular bacteria. Unfortunately, in some cases the innate immune response fails to protect the host and chronic inflammation, transplant rejection, or other disorders may occur.
- PMID:
- 22241076
- [PubMed - as supplied by publisher]
Cereulide produced by Bacillus cereus increases fitness of the producer organism in low potassium environment.
Source
Dept Food and Environmental Science, Helsinki University;
Abstract
Cereulide, produced by certain Bacillus cereus strains, is a lipophilic cyclic peptide of 1152 Da that binds K+ ions with high specificity and affinity. It is toxic to humans, but its role for the producer organism is not known. We report here that cereulide operated for B. cereus as a tool to scavenge potassium when the environment is growth limiting for this ion. Cereulide producing B. cereus showed higher maximal growth rates (µmax) than cereulide non-producing B. cereus in K+ deficient medium, [K+] ~ 1 mM. The cereulide producing strains grew faster in K+ deficient than in K+ rich medium with or without added cereulide. Cereulide non-producing B. cereus neither increased µmax in K+ deficient medium compared to K+ rich medium, nor benefited from added cereulide. Cereulide producing strains outcompeted GFP-labeled B. thuringiensis in potassium deficient ([K+] ~1 mM) but not in potassium rich ([K+] ~30 mM) medium. Exposure to 2 µM of cereulide in potassium free medium void of energy source caused within seconds a major efflux of cellular K+ from B. cereus not producing cereulide and from B. subtilis. Cereulide depleted the cereulide non-producing B. cereus and B. subtilis cells of a major part of their K+ stores, but did not affect cereulide producing B. cereus strains. Externally added 6 - 10 µM cereulide triggered generation of biofilms and pellicles by B. cereus. The results indicate that both endogenous and externally accessible cereulide supported the fitness of the cereulide producing B. cereus in environments where potassium concentration is low.
- PMID:
- 22241046
- [PubMed - as supplied by publisher]
Plasma Adrenomedullin Concentration in Dogs with Myxomatous Mitral Valvular Disease.
Source
Laboratory of Veterinary Surgery, Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University.
Abstract
Adrenomedullin (AM), a peptide identified to have vasodilating and natriuretic effects, is involved in the regulation of the cardiovascular system. To evaluate plasma AM concentration in dogs with myxomatous mitral valvular disease (MMVD), and to investigate the associations between the concentrations of plasma AM and natriuretic peptides and the echocardiographic data, we evaluated plasma AM concentrations in 31 healthy control dogs and 57 dogs with MMVD. Plasma AM concentrations in dogs with MMVD were higher than that in the control subjects. Plasma AM concentration increased in population to the severity of heart failure according to the International Small Animal Cardiac Health Council (ISACHC). AM concentrations were respectively 25.1 ± 5.0 fmol/ml (ISACHC class Ia), 29.9 ± 11.0 fmol/ml (ISACHC class Ib), 43.4 ± 19.8 fmol/ml (ISACHC class II) and 73.5 ± 21.7 fmol/ml (ISACHC class III) and 7.5 ± 5.1 fmol/ml (control group). The response-operating characteristics (ROC) curve indicated an area of 0.93 (95% CI, 0.8801-0.9889; < 0.0001), a cutoff value of 30.5 fmol/ml, a sensitivity of 87.1 %, and a specificity of 82.5 % for the determination of congestive heart failure. Plasma AM concentrations correlated with atrial natriuretic peptide concentrations, LA/Ao ratio, and left ventricular diameter. In conclusion, AM may be potential diagnostic marker for canine MMVD and possibly plays a pathophysiological role in collaboration with the other neurohumoral factors such as natriuretic peptides.
- PMID:
- 22240987
- [PubMed - as supplied by publisher]
Immunocytochemical localization of kisspeptin neurons in the rat forebrain with special reference to sexual dimorphism and interaction with GnRH neurons.
Source
Graduate School of Science and Engineering, Saitama University, Saitama 338-8570, Japan.
Abstract
Kisspeptin/metastin has been implicated as a critical regulator in luteinizing hormone (LH) secretion and the reproductive system mediating the effect of estrogen on GnRH neurons. In the present study we examined the sex differences in the effects of estrogen on Kiss1/kisspeptin expression in the forebrain by using gonadectomized rats to assess the interaction of kisspeptin and GnRH neurons. Kiss1/kisspeptin cell bodies were abundant in the rostral periventricular area of the third ventricle (RV3P) and the arcuate nucleus (ARC). A few cell bodies were also observed in other portions of the forebrain, i.e. the bed nucleus of the stria terminalis (BST), the paraventricular hypothalamic nucleus (PaAP), the ventromedial hypothalamic nucleus (VMH), and the medial amygdaloid nucleus (MeA). Kisspeptin-immunoreactive fibers were found mainly in the median eminence (ME), the ARC, and the RV3P, but were scarce in the preoptic area (POA), where GnRH neurons are localized. We also found that estrogen triggers expression of the Kiss1 gene and peptide within all the regions except the ARC, and that the effects in the RV3P, BST, PaAP, and VMH are greater in estrogen treated ovariectomized female rat. It is noteworthy that kisspeptin and GnRH neurons were densely associated in the ME but were rarely in contact in the POA. Thus, our results suggest that kisspeptin-positive neurons, except for the ones in the ARC, are related not only to estrogen-positive feedback, but also sex dimorphism, and that kisspeptin regulates GnRH release in the ME rather than the POA.
- PMID:
- 22240892
- [PubMed - as supplied by publisher]
Sonic hedgehog maintains survival and growth of chronic myeloid leukemia progenitor cells through β-catenin signaling.
Source
Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Hematology, the Affiliated Hospital of Medical College Qingdao University, Qingdao, China.
Abstract
Sonic hedgehog (Shh) signaling plays an important role in many human cancers and cancer stem cells. Here we investigate the activity and functional role of Shh signaling in chronic myeloid leukemia (CML) and leukemia progenitor cells. Differential activation of Shh signaling was found in about 50% CML-CP samples, 70% CML-AP samples and more than 80% CML-BP samples. Deregulated activation of Shh signaling was observed in CD34(+) and c-kit(+) leukemia progenitor cells. Stimulation of Shh signaling with exogenous Shh peptide induced expansion of CD34(+) and c-kit(+) progenitor cells (p<0.05), inversely, blocking the pathway with signal inhibitor induced cell apoptosis (p<0.05). Low level of Shh protein was observed in CML bone marrow stromal cells, besides, CD34(+) progenitor cells are less sensitive to exogenous Shh peptide and more sensitive to cyclopamine than CD34(-) cells (p<0.05), implying cell-autonomous activation of Shh signaling play a predominantly role in progenitor cells. Co-activation of Shh and β-catenin signaling was found in CD34(+) and c-kit(+) progenitor cells. Administration of Shh neutralizing antibody or Wnt3a neutralizing antibody in c-kit(+) progenitor cells induced cell apoptosis, however, Wnt3a peptide could salvage anti-Shh-induced cell apoptosis while Shh peptide failed to revert anti-Wnt3a-induced cell apoptosis. C-MYC, GLI1, BCL-2, P21 were also found to be downstream targets of Shh signaling, mediating apoptosis or G2/M cell cycle arrest of progenitor cells. Our results demonstrate that auto-activated Shh signaling provides survival and proliferative cues in CML progenitor cells through downstream β-catenin signaling, thus suggesting a novel therapeutic approach in CML.
Copyright © 2012 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.
- PMID:
- 22240607
- [PubMed - as supplied by publisher]
Insulin Sensitivity After Maximal and Endurance Resistance Training.
Source
1Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway; 2Faculty of Education, Nord-Trøndelag University College, Levanger, Norway; 3Department of Health Science, Nord-Trøndelag University College, Levanger, Norway; 4Department of Health Sciences, Mid Sweden University, Östersund, Sweden; and 5Hormone Laboratory, Oslo University Hospital-Aker, Oslo, Norway.
Abstract
Hansen, E, Landstad, BJ, Gundersen, KT, Torjesen, PA, and Svebak, S. Insulin sensitivity after maximal and endurance resistance training. J Strength Cond Res 26(2): 327-334, 2012-The purpose of the study was to compare the effects of maximal resistance training (MRT) vs. endurance resistance training (ERT) on improvements in insulin levels and glucose tolerance in overweight individuals at risk of developing type 2 diabetes. Eighteen participants with baseline values suggesting impaired glucose tolerance were randomly assigned to 1 of 2 groups. Group 1 engaged in supervised MRT (Bernstein inverted pyramid system: 5 × 3-4, 60-85% 1 repetition maximum [1RM]), 3 d·wk over 4 months, whereas members of group 2 acted as controls. Later, group 2 engaged in supervised ERT (3 × 12-15, 45-65% 1RM), 3 d·wk over a 4 month period with the 2 prebaselines as controls. Both interventions consisted of 8 exercises that included the entire body. Glucose (fasting and 2-hour test), insulin and C-peptide measures were assessed from pre to post in both groups. The MRT led to reduced blood levels of 2-hour glucose (p = 0.044) and fasting C-peptide (p = 0.023) and decreased insulin resistance (p = 0.040). The ERT caused a significant reduction in the blood levels of insulin (p = 0.023) and concomitant positive effects on % insulin sensitivity (p = 0.054) and beta-cell function (p = 0.020). The findings indicate that both MRT and ERT lead to decreased insulin resistance in people with a risk of developing type 2 diabetes; MRT led to a greater increase in glucose uptake capacity (in muscles), whereas ERT led to greater insulin sensitivity, supporting the recommendation of both MRT and ERT as primary intervention approaches for individuals at a risk of developing type 2 diabetes.
- PMID:
- 22240549
- [PubMed - as supplied by publisher]
The Antibiotic Thermorubin Inhibits Protein Synthesis by Binding to Inter-Subunit Bridge B2a of the Ribosome.
Source
Department of Chemistry, Yale University, 225 Prospect Street, PO Box 208107, New Haven, CT 06520-8107, USA.
Abstract
Thermorubin is a small-molecule inhibitor of bacterial protein synthesis, but relatively little is known about the molecular mechanism by which it blocks translation. The structure of the complex between thermorubin and the 70S ribosome from Thermus thermophilus reported here shows that thermorubin interacts with the ribosome in a way that is distinct from any other known class of ribosome inhibitor. Though it is structurally similar to tetracycline, it binds to the ribosome at an entirely different location-the interface between the small and large subunits that is formed by inter-subunit bridge B2a. This region of the ribosome is known to play a role in the initiation of translation, and thus, the binding site we observe is consistent with evidence suggesting that thermorubin inhibits the initiation stage of protein synthesis. The binding of thermorubin induces a rearrangement of two bases on helix 69 of the 23S rRNA, and presumably, this rearrangement blocks the binding of an A-site tRNA, thereby inhibiting peptide bond formation. Due in part to its low solubility in aqueous media, thermorubin has not been used clinically, although it is a potent antibacterial agent with low toxicity (Therapeutic Index>200). The interactions between thermorubin and the ribosome, as well as its adjacency to the observed binding sites of three other antibiotic classes, may enable the design of novel derivatives that share thermorubin's mode of action but possess improved pharmacodynamic properties.
No comments:
Post a Comment