C-type natriuretic peptide and brain natriuretic peptide inhibit adenylyl cyclase activity: interaction with ANF-R2/ANP-C receptors

AbstractC-type natriuretic peptide (CNP) and brain natriuretic peptide (BNP) are members of the natriuretic peptide family, which have been shown to interact with ANP-C/ANF-R2 receptors in addition to ANP-B receptor subtypes. The present study was undertaken to investigate if the interaction of CNP and BNP with ANP-C receptors results in the inhibition of adenylyl cyclase activity. CNP and BNP inhibited adenylyl cyclase activity in heart and brain striatal membranes in a concentration dependent manner with an apparent Ki between 0.1 and 1.0 nM. Maximal inhibition observed in heart membranes were about 25% and 35% for BNP and CNP respectively, however the inhibitions in brain striatal membranes were smaller (∼2%). The inhibition was dependent on the presence of guanine nucleotides and was attenuated by pertussis toxin treatment. In addition, CNP inhibited the stimulatory effect of isoproterenol on adenylyl cyclase, whereas CNP as well as BNP showed an additive effect with the inhibitory response of angiotensin II on adenylyl cyclase activity. When the combined effect of C-ANF4−23/BNP, C-ANF4−23/CNP and BNP/CNP at optimal concentrations was studied together on adenylyl cyclase activity, the percent inhibition remained the same for C-ANF4−23 and BNP or C-ANF4−23 and CNP, however, an additive inhibitory effect was observed for BNP and CNP. These results suggest that CNP and BNP like C-ANF4−23 interact with ANP-C receptors and result in the inhibition of adenylyl cyclase activity. On the other hand, CNP and BNP interact with the ANP-C receptor, however, the interaction may be at different sites or there may be two subpopulations of ANP-C receptors specific for each of the peptides. These results indicate that BNP and CNP, like ANP and C-ANF4−23, inhibit the adenylyl cyclase/cAMP signal transduction system through an inhibitory guanine nucleotide regulatory protein, by interacting with ANP-C receptor subtypes

Increased vulnerability of nigral dopamine neurons after expansion of their axonal arborization size through D2 dopamine receptor conditional knockout

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNc). Rare genetic mutations in genes such as Parkin, Pink1, DJ-1, α-synuclein, LRRK2 and GBA are found to be responsible for the disease in about 15% of the cases. A key unanswered question in PD pathophysiology is why would these mutations, impacting basic cellular processes such as mitochondrial function and neurotransmission, lead to selective degeneration of SNc DA neurons? We previously showed in vitro that SNc DA neurons have an extremely high rate of mitochondrial oxidative phosphorylation and ATP production, characteristics that appear to be the result of their highly complex axonal arborization. To test the hypothesis in vivo that axon arborization size is a key determinant of vulnerability, we selectively labeled SNc or VTA DA neurons using floxed YFP viral injections in DAT-cre mice and showed that SNc DA neurons have a much more arborized axon than those of the VTA. To further enhance this difference, which may represent a limiting factor in the basal vulnerability of these neurons, we selectively deleted in mice the DA D2 receptor (D2-cKO), a key negative regulator of the axonal arbour of DA neurons. In these mice, SNc DA neurons have a 2-fold larger axonal arborization, release less DA and are more vulnerable to a 6-OHDA lesion, but not to α-synuclein overexpression when compared to control SNc DA neurons. This work adds to the accumulating evidence that the axonal arborization size of SNc DA neurons plays a key role in their vulnerability in the context of PD

A prospective, multi-centric, observational registry to evaluate performance of Excel™ DES in ‘Real World, All Comers’ patient population

AbstractObjectivesThis study aims to assess the safety and efficacy of a biodegradable polymer-coated Rapamycin-Eluting Stent (Excel) used in conjunction with six-month dual antiplatelet therapy in daily practice.BackgroundThe polymeric material of cardiac stents has been reported to adversely affect the safety profile of the drug-eluting stents and is also suspected to cause serious long-term complications. It has been proposed that the biodegradable polymer coatings may reduce such late-stage adverse effects.MethodsThis is a prospective, multi-center registry of 654 patients from across 9 cardiology centers in India, who were enrolled and exclusively treated with Excel stents between February 2008 and May 2010. The recommended antiplatelet regimen included clopidogrel and aspirin for 6 months period, followed by lifelong aspirin therapy.ResultsThe study population included 46.94% diabetics, 24.31% smokers, 48.93% hypertensives and 14.98% hyperlipidemics. The cumulative rates of major adverse cardiac events were 0.153% at discharge and 1.38% at 12 months. The mean percentage of stenosis was 88.24 ± 9.17% No events occurred between 6 and 12 months.ConclusionsThis multi-center registry study on “real world, all comers” has, thus, showed that EXCEL™ stent which is PLA-coated biodegradable Rapamycin-Eluting Stent exhibited high efficacy and safety profile in treatment of patients undergoing PCI as evidenced by significantly lower rates of MACE and no case of stent thrombosis. There was no event even after DAPT was discontinued after 6 months

Laminar flow heat transfer enhancement in square and rectangular channels having : (1) A wire-coil, axial and spiral corrugation combined with helical screw-tape with and without oblique teeth and a (2) spiral corrugation combined with twisted tapes with oblique teeth

Heat transfer enhancement is a vital area of research as it helps to design heat exchangers of reduced sizes and improved heat transfer rates. Thus, there is a pressing need for techniques which result in significantly increased heat transfer over and above increased pressure drop. In this paper, the benefits of different compound techniques using (1) wire-coil inserts and helical screw-tape inserts with oblique teeth, (2) wire-coil inserts and helical screw-tape inserts without oblique teeth, (3) spiral corrugation and helical screw-tape inserts without oblique teeth, (4) axial corrugation and helical screw-tape inserts without oblique teeth, and (5) spiral corrugation and twisted-tape inserts with oblique teeth were studied experimentally for laminar flow in a non-circular duct (aspect ratio = 1, 0.5 and 0.33). Servotherm medium oil with Prandtl number ranging from 430 to 530 was used as working fluid. The experiment was conducted for a uniform heat flux boundary condition. The effect of geometric parameters of the inserts such as wire-coil diameter, wire-coil helix angle, tooth angle and tooth horizontal length of the screw tape and the twisted tape, corrugation height and corrugation pitch, etc. on heat transfer and pressure drop characteristics was presented. The influence of duct geometry (aspect ratio) on Nusselt number and friction factor was also studied. Correlations for Nusselt number and friction factor were developed and a performance evaluation was done.AICTE [20/AICTE/RIFD/RPS (Policy II): 84/2012-2013]; UGC [UGC 41-989/2012 (SR)]; DST [SR/S3/MERC-0045/2010(G)]; CSIR [22(0386)/05/EMR-II] and the Government of India.http://www.elsevier.com/locate/ijhmt2020-12-01hj2019Mechanical and Aeronautical Engineerin

Babesia microti, Upstate New York

Five cases of human babesiosis were reported in the Lower Hudson Valley Region of New York State in 2001. An investigation to determine if Babesia microti was present in local Ixodes scapularis ticks yielded 5 positive pools in 123 pools tested, the first detection of B. microti from field-collected I. scapularis in upstate New York