370 research outputs found

    Involvement of β3-Adrenoceptor in Altered β-Adrenergic Response in Senescent Heart: Role of Nitric Oxide Synthase 1–derived Nitric Oxide

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    Background: In senescent heart, β-adrenergic response is altered in parallel with β1- and β2-adrenoceptor down-regulation. A negative inotropic effect of β3-adrenoceptor could be involved. In this study, the authors tested the hypothesis that β3-adrenoceptor plays a role in β-adrenergic dysfunction in senescent heart.Methods: β-Adrenergic responses were investigated in vivo (echocardiography–dobutamine, electron paramagnetic resonance) and in vitro (isolated left ventricular papillary muscle, electron paramagnetic resonance) in young adult (3-month-old) and senescent (24-month-old) rats. Nitric oxide synthase (NOS) immunolabeling (confocal microscopy), nitric oxide production (electron paramagnetic resonance) and β-adrenoceptor Western blots were performed in vitro. Data are mean percentages of baseline ± SD. Results: An impaired positive inotropic effect (isoproterenol) was confirmed in senescent hearts in vivo (117 ± 23 vs. 162 ± 16%; P < 0.05) and in vitro (127 ± 10 vs. 179 ± 15%; P < 0.05). In the young adult group, the positive inotropic effect was not significantly modified by the nonselective NOS inhibitor NG-nitro-l-arginine methylester (l-NAME; 183 ± 19%), the selective NOS1 inhibitor vinyl-l-N-5(1-imino-3-butenyl)-l-ornithine (l-VNIO; 172 ± 13%), or the selective NOS2 inhibitor 1400W (183 ± 19%). In the senescent group, in parallel with β3-adrenoceptor up-regulation and increased nitric oxide production, the positive inotropic effect was partially restored by l-NAME (151 ± 8%; P < 0.05) and l-VNIO (149 ± 7%; P < 0.05) but not by 1400W (132 ± 11%; not significant). The positive inotropic effect induced by dibutyryl-cyclic adenosine monophosphate was decreased in the senescent group with the specific β3-adrenoceptor agonist BRL 37344 (167 ± 10 vs. 142 ± 10%; P < 0.05). NOS1 and NOS2 were significantly up-regulated in the senescent rat. Conclusions: In senescent cardiomyopathy, β3-adrenoceptor overexpression plays an important role in the altered β-adrenergic response via induction of NOS1-nitric oxide

    Cutting dipping application of Flupyradifurone against cassava whiteflies Bemisia tabaci and impact on its parasitism in cassava

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    Open Access JournalThe cassava whitefly Bemisia tabaci causes damage in cassava through the feeding and vectoring of plant viruses that cause cassava mosaic and cassava brown streak diseases. This study sought to explore the efficacy of cutting dipping in flupyradifurone for whitefly control and the impact of the mode of application on whitefly parasitism under farmer field conditions. The insecticide treatment significantly reduced adult whiteflies by 41%, nymphs by 64%, and cassava mosaic disease (CMD) incidence by 16% and increased root yield by 49%. The whitefly parasitism rate by Encarsia spp. parasitoids was 27.3 and 21.1%, while Eretmocerus spp. had 26.7 and 18.0% in control and flupyradifurone, respectively, and these differences were not significant. Electropenetrography recordings of whitefly feeding behaviour on flupyradifurone-treated plants showed significantly reduced probing activity and a delay in reaching the phloem as compared to the control. The findings from this study demonstrated that cassava cutting dipping in flupyradifurone significantly reduces whitefly numbers and cassava mosaic disease incidence, thus contributing to a significant root yield increase in cassava. Flupyradifurone applied through cutting dips does not significantly impact parasitism rates in cassava fields. Routine monitoring of parasitoids and predators in insecticide-treated versus control fields should be emphasized to determine the impact of pesticides on these beneficial non-target organisms

    Expression profiling of metalloproteinases and tissue inhibitors of metalloproteinases in normal and degenerate human achilles tendon

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    To profile the messenger RNA (mRNA) expression for the 23 known genes of matrix metalloproteinases (MMPs), 19 genes of ADAMTS, 4 genes of tissue inhibitors of metalloproteinases (TIMPs), and ADAM genes 8, 10, 12, and 17 in normal, painful, and ruptured Achilles tendons. Tendon samples were obtained from cadavers or from patients undergoing surgical procedures to treat chronic painful tendinopathy or ruptured tendon. Total RNA was extracted and mRNA expression was analyzed by quantitative real-time reverse transcription–polymerase chain reaction, normalized to 18S ribosomal RNA. In comparing expression of all genes, the normal, painful, and ruptured Achilles tendon groups each had a distinct mRNA expression signature. Three mRNA were not detected and 14 showed no significant difference in expression levels between the groups. Statistically significant (P < 0.05) differences in mRNA expression, when adjusted for age, included lower levels of MMPs 3 and 10 and TIMP-3 and higher levels of ADAM-12 and MMP-23 in painful compared with normal tendons, and lower levels of MMPs 3 and 7 and TIMPs 2, 3, and 4 and higher levels of ADAMs 8 and 12, MMPs 1, 9, 19, and 25, and TIMP-1 in ruptured compared with normal tendons. The distinct mRNA profile of each tendon group suggests differences in extracellular proteolytic activity, which would affect the production and remodeling of the tendon extracellular matrix. Some proteolytic activities are implicated in the maintenance of normal tendon, while chronically painful tendons and ruptured tendons are shown to be distinct groups. These data will provide a foundation for further study of the role and activity of many of these enzymes that underlie the pathologic processes in the tendon

    Deficiency and Also Transgenic Overexpression of Timp-3 Both Lead to Compromised Bone Mass and Architecture In Vivo

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    Tissue inhibitor of metalloproteinases-3 (TIMP-3) regulates extracellular matrix via its inhibition of matrix metalloproteinases and membrane-bound sheddases. Timp-3 is expressed at multiple sites of extensive tissue remodelling. This extends to bone where its role, however, remains largely unresolved. In this study, we have used Micro-CT to assess bone mass and architecture, histological and histochemical evaluation to characterise the skeletal phenotype of Timp-3 KO mice and have complemented this by also examining similar indices in mice harbouring a Timp-3 transgene driven via a Col-2a-driven promoter to specifically target overexpression to chondrocytes. Our data show that Timp-3 deficiency compromises tibial bone mass and structure in both cortical and trabecular compartments, with corresponding increases in osteoclasts. Transgenic overexpression also generates defects in tibial structure predominantly in the cortical bone along the entire shaft without significant increases in osteoclasts. These alterations in cortical mass significantly compromise predicted tibial load-bearing resistance to torsion in both genotypes. Neither Timp-3 KO nor transgenic mouse growth plates are significantly affected. The impact of Timp-3 deficiency and of transgenic overexpression extends to produce modification in craniofacial bones of both endochondral and intramembranous origins. These data indicate that the levels of Timp-3 are crucial in the attainment of functionally-appropriate bone mass and architecture and that this arises from chondrogenic and osteogenic lineages

    Lieb-Robinson Bounds for the Toda Lattice

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    We establish locality estimates, known as Lieb-Robinson bounds, for the Toda lattice. In contrast to harmonic models, the Lieb-Robinson velocity for these systems do depend on the initial condition. Our results also apply to the entire Toda as well as the Kac-van Moerbeke hierarchy. Under suitable assumptions, our methods also yield a finite velocity for certain perturbations of these systems

    Automorphic Equivalence within Gapped Phases of Quantum Lattice Systems

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    Gapped ground states of quantum spin systems have been referred to in the physics literature as being `in the same phase' if there exists a family of Hamiltonians H(s), with finite range interactions depending continuously on s[0,1]s \in [0,1], such that for each ss, H(s) has a non-vanishing gap above its ground state and with the two initial states being the ground states of H(0) and H(1), respectively. In this work, we give precise conditions under which any two gapped ground states of a given quantum spin system that 'belong to the same phase' are automorphically equivalent and show that this equivalence can be implemented as a flow generated by an ss-dependent interaction which decays faster than any power law (in fact, almost exponentially). The flow is constructed using Hastings' 'quasi-adiabatic evolution' technique, of which we give a proof extended to infinite-dimensional Hilbert spaces. In addition, we derive a general result about the locality properties of the effect of perturbations of the dynamics for quantum systems with a quasi-local structure and prove that the flow, which we call the {\em spectral flow}, connecting the gapped ground states in the same phase, satisfies a Lieb-Robinson bound. As a result, we obtain that, in the thermodynamic limit, the spectral flow converges to a co-cycle of automorphisms of the algebra of quasi-local observables of the infinite spin system. This proves that the ground state phase structure is preserved along the curve of models H(s),0s1H(s), 0\leq s\leq 1.Comment: Updated acknowledgments and new email address of S

    The measurement of ancestral roots with genealogical data

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    This study presents a new method to measure the depth of ancestral roots in a population. This method sheds light on the migratory movements which led to present-day population distribution across space. The method was applied to a dataset of 5,100 ascending genealogies from seventeen regions of the province of Quebec (Canada). Dates of marriage of the earliest ancestors married in the same region as their descendants were used to measure the age of individual ancestral roots. The average regional ages vary between 16 and 157 years, while some individual roots reach as far back as 300 years in the same region. The proposed method can be useful for assessing how deeply rooted a contemporary population is at a local, regional or other geographical level

    Sinteza i farmakološka evaluacija 3-cikloheksil-2-supstituiranih hidrazino-3H-kinazolin-4-ona kao analgetika i antiinflamatorika

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    A series of novel 3-cyclohexyl-2-substituted hydrazino-quinazolin-4(3H)-ones were synthesized by reacting the amino group of 3-cyclohexyl-2-hydrazino quinazolin-4(3H)-one with a variety of aldehydes and ketones. The starting material, 3-cyclohexyl-2-hydrazino quinazolin-4(3H)-one, was synthesized from cyclohexyl amine. Title compounds were investigated for analgesic, anti-inflammatory and ulcerogenic behavior. The compound 3-cyclohexyl-2-(1-methylbutylidene-hydrazino)-3H-quinazolin-4-one (4c) emerged as the most active compound of the series and is moderately more potent in its analgesic and anti-inflammatory activities compared to the reference standard diclofenac sodium. Interestingly, test compounds showed only mild ulcerogenic potential when compared to acetylsalicylic acid.Reakcijom amino skupine 3-cikloheksil-2-hidrazino kinazolin-4(3H)-ona s različitim aldehidima i ketonima sintetizirani su novi 3-cikloheksil-2-supstituirani hidrazino-kinazolin-4(3H)-oni. Početni spoj 3-cikoheksil-2-hidrazino kinazolin-4(3H)-on pripravljen je iz cikloheksilamina. Sintetizirani spojevi testirani su na analgetsko i protuupalno djelovanje te ulcerogena svojstva. Spoj 3-cikloheksil-2-(1-metilbutiliden-hidrazino)-3H-kinazolin-4-on (4c) imao je najjače analgetsko i protuupalno djelovanje, nešto jače nego referentni spoj diklofenak natrij. Osim toga, testirani spojevi imaju samo blago ulcerogeno djelovanje u usporedbi s acetilsalicilnom kiselinom

    Primary hyperparathyroidism: review and recommendations on evaluation, diagnosis, and management. A Canadian and international consensus

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    The purpose of this review is to assess the most recent evidence in the management of primary hyperparathyroidism (PHPT) and provide updated recommendations for its evaluation, diagnosis and treatment. A Medline search of "Hyperparathyroidism. Primary" was conducted and the literature with the highest levels of evidence were reviewed and used to formulate recommendations. PHPT is a common endocrine disorder usually discovered by routine biochemical screening. PHPT is defined as hypercalcemia with increased or inappropriately normal plasma parathyroid hormone (PTH). It is most commonly seen after the age of 50 years, with women predominating by three to fourfold. In countries with routine multichannel screening, PHPT is identified earlier and may be asymptomatic. Where biochemical testing is not routine, PHPT is more likely to present with skeletal complications, or nephrolithiasis. Parathyroidectomy (PTx) is indicated for those with symptomatic disease. For asymptomatic patients, recent guidelines have recommended criteria for surgery, however PTx can also be considered in those who do not meet criteria, and prefer surgery. Non-surgical therapies are available when surgery is not appropriate. This review presents the current state of the art in the diagnosis and management of PHPT and updates the Canadian Position paper on PHPT. An overview of the impact of PHPT on the skeleton and other target organs is presented with international consensus. Differences in the international presentation of this condition are also summarized
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