Cell death triggered by frataxin knockdown can be impaired by interference with p53, caspase inhibitors and gene transfer of FXN. These results suggest that frataxin gene silencing in human neuron-like cells may constitute a useful cell model to characterize the molecular changes triggered by frataxin deficiency in neurons, as well as to search for therapies that may protect against neurodegeneration.”
“We Momelotinib manufacturer propose a new hemodynamic index for the initiation of a cerebral aneurysm, defined by the temporal fluctuations of tension/compression forces acting on endothelial cells. We employed a patient-specific geometry of a human internal

carotid artery (ICA) with an aneurysm, and reconstructed the geometry of the ICA before aneurysm formation by artificially removing the aneurysm. We calculated the proposed hemodynamic index and five other hemodynamic indices (wall shear stress (WSS) at peak systole, time-averaged WSS, time-averaged spatial WSS gradient, oscillatory shear index (OSI), and potential aneurysm formation indicator (AFI)) for the geometry before aneurysm formation using a computational fluid dynamics technique. By comparing the distribution of each index at the location of aneurysm formation, we discussed the validity of each. The results showed that only the proposed hemodynamic index had a significant correlation with the

location of aneurysm formation.

Our findings suggest that the proposed index may be useful as a hemodynamic index for the initiation of cerebral aneurysms. (c) 2008 Elsevier Ltd. All rights reserved.”
“We SIS3 investigated prolactin secretion and metabolic changes in stress response in adult male rats submitted to periodic maternal separation (MS; 180 min/day) at 2 weeks of life. Restraint and ether exposure were randomly performed when the animals were 10-12 weeks of age. Restraint exposure: the animals were placed into plastic tubes (21 cm long, 4.5 cm diameter) for 20 min. Ether exposure: the rats were exposed to ether for 10 min. Atrial cannulation for blood sampling was performed through the jugular vein 5 days before the experiments. In both protocols, blood samples were taken immediately before 4-Hydroxytamoxifen cost (0), and 5, 15 and 20 min after the beginning of stress exposure. Ours results showed attenuated endocrine and metabolic responses to ether exposure in the maternal separation (MS) group compared to the control group. The measured metabolic parameters, plasma glucose, prolactin, lactate, and insulin secretion, were 32%, 55%, 41%, 73% lower (P<0.01), respectively, in MS than in control animals. On the other hand, the endocrine and metabolic stress responses to restraint exposure were not affected by maternal separation. There was no difference between the MS and the control groups in any of the parameters studied.

(C) 2013 Elsevier B.V. All rights reserved.”
“The definitive diagnosis ON-01910 ic50 ability of IgM ELISA, nested RT-PCR and real-time quantitative PCR (qPCR) was evaluated for Chikungunya diagnosis using 180 clinical samples. Real-time qPCR showed a higher sensitivity (88.3%) for Chikungunya

diagnosis in the early stages of infection, while IgM ELISA proved sensitive for the late stages of illness (81.8%). The results suggest that the application of both IgM ELISA and RT-PCR based assays will be ideal for definitive diagnosis of Chikungunya during outbreaks.”
“The chloroplast bioreactor is an alternative to fermentation-based systems for production of vaccine antigens and biopharmaceuticals. We report here expression of the plague FIN fusion antigen in chloroplasts. Site-specific transgene integration and homoplasmy were confirmed by PCR and Southern blotting. Mature leaves showed the highest level of transgene expression on the third day of continuous illumination, with a maximum level of 14.8% of the total soluble protein. Swiss Webster mice were primed with adjuvant-containing subcutaneous (s.c.) doses of F1-V and then boosted with either adjuvanted s.c. doses (s.c. FIN mice) or unadjuvanted oral doses (oral F1-V mice). Oral FIN mice had higher prechallenge serum immunoglobulin G1 (IgG1) titers than s.c. F1-V mice. The corresponding serum levels of antigen-specific IgG2a and IgA were

2 and 3 orders of magnitude lower, respectively. selleck chemicals After vaccination, mice were exposed to an inhaled dose of 1.02 X 10(6) CFU of aerosolized Yersinia pestis CO92 (50% lethal dose, 6.8 X 10(4) CFU). All control animals died within 3 days. F1-V given s.c. (with adjuvant) protected 33% of the immunized mice, while 88% of the oral F1-V mice survived aerosolized Y. pestis challenge. A comparison of splenic Y. pestis CFU counts showed that there was a 7-

to 10-log reduction in the mean bacterial burden in survivors. Taken together, these data indicate that oral booster doses effectively elicit protective immune responses in vivo. In addition, this is the first report of a plant-derived oral vaccine that protected animals from live Y. pestis challenge, bringing the likelihood of lower-cost vaccines SN-38 closer to reality.”
“Hydroxyapatite-polymer composite materials, as biological bone tissue materials, have become an important research direction. In this paper, the calcium carbonate from the crabshells was transformed into hydroxyapatite by a hydrothermal process. According to the method that we called Biomorphic Mineralization synthesis, we obtained a novel kind of hydroxyapatite-chitosan composite materials which reserved the natural perfect structure of the original crabshells. Benefited from its fine micro-structure as the crabshells, this kind of materials held a high value of tensile modulus, which is expected to be promising bone tissue engineering applications.

Methods: We compared 5 groups of male adult Wistar albino rats: a control group, an untreated diabetic group, and diabetic groups treated with perindopril, catechin, or catechin + perindopril. Results: Blood glucose values in all diabetic groups were significantly higher than in the control group (p smaller than 0.001). The body weight in all diabetic groups was significantly lower than in the control group (p smaller than 0.001, p smaller than 0.05). The kidney weight in the catechin + perindopril-treated diabetic group was significantly lower than in the untreated diabetic group (p smaller than 0.001). In all treated diabetic groups, Ma levels decreased significantly

(p smaller than 0.001). Mesangial selleck inhibitor matrix and podocyte damage increased in the untreated diabetic group, but the group treated with catechin + perindopril showed less damage. TGFbeta 1 immunostaining was significantly lower in the catechin-treated and perindopril-treated groups than in the untreated diabetic group (p smaller than 0.001). Catechin was more effective than ACEI in preventing podocyte structure. Podocytes appeared to be the first cells affected in diabetes mellitus. When exposed to hyperglycemia, podocytes caused the

mesangial matrix to expand. Conclusions: www.selleckchem.com/products/dorsomorphin-2hcl.html Catechin and perindopril were more effective in preventing renal corpuscle damage when administered together. (C) 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.”
“Objectives: To study the impact of tendon transfer surgery for ulnar claw hand correction in children with leprosy. Subjects and Methods: All the children who underwent reconstructive surgery for ulnar BMS-777607 nmr nerve paralysis during the period 2007 to 2012 were included in the study. Unassisted angle, grasp contact, pinch contact and functional assessment were the main outcome measures. All the surgical procedures were performed by the same surgeon and pre- and post-operative therapy protocol was same for all the patients.

A common surgical audit form was used to record assessments for all the patients. Results: In this case series, 82 hands of 79 patients with ulnar paralysis were included. All the children had lasso surgery. In 83% of hands, flexor digitorum superficialis of middle or ringer finger was used, while in the remaining patients palmaris longus or extensor carpi radialis longus with fascia lata graft was used as the motor tendon. The unassisted angle decreased in all the patients, indicating correction of claw fingers. Hand function improved after surgery and it showed steady progress during follow-up. Conclusion: The deformity due to leprosy in the hands of children is a tragedy as it hampers the use of hands in daily routine activities, school work and other social interactions.

This strategy avoids

conventional solid-phase immobilization owing to its inherent potential for denaturation of the antigen. In addition, a functional screening strategy selects single-chain variable fragments (scFvs) directly for their capacity for both specific binding and stabilization of the target enzyme in its inactive conformation. These conformation-specific scFvs illustrate that stabilization of oxidized PTP1B is an effective strategy to inhibit PTP1B function; it is possible that this approach may be applicable to the protein tyrosine phosphatase (PTP) family as a whole. With this protocol, isolation and characterization of specific scFvs from immune responsive animals should take similar to 6 weeks.”
“Type 1 regulatory T (Tr1) cells are an inducible subset of CD4(+) Tr cells characterized by high levels STI571 price of interleukin

(IL)-10 production and regulatory properties. Several protocols to generate human Tr1 cells have been developed in vitro. However, the resulting population includes a significant fraction of contaminating non-Tr1 cells, representing a major bottleneck for clinical application of Tr1 cell therapy. We generated an homogeneous IL-10 producing Tr1 cell population by transducing human CD4(+) T cells with a bidirectional lentiviral vector (LV) encoding for human IL-10 and the marker gene, green fluorescent protein (GFP), which are independently coexpressed. The resulting GFP(+) LV-IL-10-transduced human CD4(+) T (cD4(LV-IL-10)) cells expressed, upon Ricolinostat supplier T-cell receptor (TCR) activation, high levels of IL-10 and concomitant low levels selleck of IL-4, and markers associated with IL-10. Moreover, cD4(LV-IL10) T cells displayed typical Tr1 features: the anergic phenotype, the IL-10, and transforming growth factor (TGF)-beta dependent suppression of allogeneic T-cell responses, and the ability to suppress in a cell-to-cell contact independent manner in vitro. CD4(LV-IL-10) T cells were able to control xeno graft-versus-host disease (GvHD), demonstrating their suppressive function in vivo. These results show that

constitutive over-expression of IL-10 in human CD4(+) T cells leads to a stable cell population that recapitulates the phenotype and function of Tr1 cells.”
“It is known that aberrant sialylation of IgA1 is involved in the pathogenesis of IgA nephropathy (IgAN). We hypothesize that aberrant sialylation of serum IgA1 may result from changes in the activity of alpha 2,6-sialyltransferase (alpha 2,6-ST) or expression of its coding gene ST6GALNAC2 in peripheral B lymphocytes. Sixty patients with IgAN and 20 healthy controls were enrolled. Peripheral B lymphocytes were isolated by CD-19-positive magnetic beads. The expression level of ST6GALNAC2 was quantitatively analysed by real-time reverse-transcriptase polymerase chain reaction (PCR).

(C) 2012 Wiley Periodicals, Inc. Develop Neurobiol 72: 9901005, 2012″
“Liposarcomas (LS) are mesenchymal tumors that can recur after surgical resection and often do not respond to presently GSK2126458 order available medical therapies. This study demonstrates the dependence of LS on de novo long-chain fatty acid synthesis for growth. Lipogenesis can be impaired by inhibiting the activities of lipogenic enzymes. including acetyl CoA-carboxylase (ACC) and fatty acid synthase (FASN), or by suppressing the expression of key genes involved in the pathway and its regulation The FASN inhibitors cerulenin and orlistat reduced the growth of two

LS cell lines (LiSa2. SW872). as did inhibition of ACC with soraphen A CDDO-Me. a synthetic triterpenoid. suppressed expression of Spot 14 and FASN genes and likewise inhibited LS cell growth Importantly. the anti-proliferative effect of each agent was prevented by the co-administration of palmitate, the major product of cellular long-chain fatty acid synthesis. In stark contrast to LS cells, these compounds had no effect on the growth of fibroblasts

Four biochemically distinct agents that target critical GW786034 points in the fatty acid synthetic pathway exert anti-proliferative effects on LS cells, and rescue of cell growth by palmitic acid suggests that reduced tumor cell lipogenesis mediates the growth inhibition These findings warrant further studies aimed at the clinical exploitation of the dependence of LS cell growth on fatty acids”
“A topological insulator is the state of quantum matter possessing

gapless spin-locking surface states across the bulk band gap, which has created new opportunities from novel electronics to energy conversion. However, the large concentration of bulk residual carriers has been a major challenge for revealing the property of the topological surface state by electron transport find more measurements. Here we report the surface-state-dominant transport in antimony-doped, zinc oxide-encapsulated Bi2Se3 nanoribbons with suppressed bulk electron concentration. In the nanoribbon with sub-10-nm thickness protected by a zinc oxide layer, we position the Fermi levels of the top and bottom surfaces near the Dirac point by electrostatic gating, achieving extremely low two-dimensional carrier concentration of 2×10(11) cm(-2). The zinc oxide-capped, antimony-doped Bi2Se3 nanostructures provide an attractive materials platform to study fundamental physics in topological insulators, as well as future applications.”
“The nuclear arsenal and the use of nuclear technologies have enhanced the likelihood of whole-body/partial-body radiation exposure. The central nervous system is highly susceptible to even low doses of radiation.

Among the large number of neuropeptides and neuromodulators implicated in these visceral pathways is neuropeptide Y (NPY), which is oftentimes colocalized in catecholaminergic DZNeP neurons themselves implicated in glucoprivic-induced feeding and satiety. In addition to the cNST and ventrolateral medulla, noradrenergic and NPY receptors are found in circumscribed regions of the medullary

reticular formation rich in preoromotor neurons. To test the hypothesis that NPY may act as a neuromodulator on preoromotor neurons, we recorded the effects of bath application of NPY and specific Y1 and Y2 agonists on currents elicited from electrical stimulation of the rostral (taste) NST in prehypoglossal neurons in a brain stem slice preparation. A high proportion of NST-driven responses were suppressed by NPY, as well as Y1 and Y2 agonists. On the basis of paired pulse ratios and changes in membrane resistance, we concluded that Y1 receptors influence these neurons both presynaptically and postsynaptically and that Y2 receptors have a presynaptic locus.

To test the hypothesis that NPY may act in concert with norepinephrine (NE), we examined neurons showing suppressed responses in the presence of a Y2 agonist and demonstrated a greater degree of suppression to a Y2 agonist/NE cocktail. These suppressive effects on preoromotoneurons may reflect a satiety pathway originating from A2 neurons in the caudal brain stem.”
“The impending influenza virus pandemic requires global

vaccination Selleck Linsitinib to prevent large-scale mortality and morbidity, but traditional influenza virus vaccine production is too slow for rapid responses. We have developed bacterial systems for expression and purification of properly folded functional hemagglutinin as a rapid response to emerging pandemic strains. A recombinant H5N1 Selleck Dinaciclib (A/Vietnam/1203/2004) hemagglutinin globular domain (HA1) was produced in Escherichia coli under controlled redox refolding conditions. Importantly, the properly folded HA1(1-320), i.e., HA1 lacking amino acids 321 to 330, contained >= 75% functional oligomers without addition of foreign oligomerization sequence. Site-directed mutagenesis mapped the oligomerization signal to the HA1 N-terminal Ile-Cys-Ile residues at positions 3 to 5. The purified HA1 oligomers (but not monomers) bound fetuin and agglutinated red blood cells. Upon immunization of rabbits, the oligomeric HA1(1-320) elicited potent neutralizing antibodies against homologous and heterologous H5N1 viruses more rapidly than HA1(28-320) containing only monomers. Ferrets vaccinated with oligomeric HA1 (but not monomeric HA1 with the N terminus deleted) at 15 and 3 mu g/dose were fully protected from lethality and weight loss after challenge with homologous H5N1 (A/Vietnam/1203/2004, clade 1) virus, as well as heterologous clade 2.2 H5N1 (A/WooperSwan/Mongolia/244/2005) virus.

Many 3-deazaneplanocin A in vivo variants of uncertain importance were reported.\n\nInterpretation Although challenges remain, our results suggest that whole-genome sequencing can yield useful and clinically relevant information for individual patients.”
“Introduction: The lower moiety of duplex kidney can be associated with ureteropelvic junction obstruction (UPJO). Surgical correction can be challenging in cases of incomplete duplication where the junction of the lower and upper pole ureters is proximal.

We review our experience with this unusual entity with an emphasis on surgical techniques employed in reconstruction.\n\nMethods: We retrospectively reviewed the charts of eight patients with lower pole UPJO who underwent surgery in 2002-2008. The surgical approach, specifically the utilization of the non-obstructed upper pole ureter, used in the reconstruction was noted.\n\nResults: Four of eight patients were symptomatic at presentation with either infection or pain. UPJO was at least in part secondary to lower pole crossing vessels

in four patients and was treated with dismembered pyeloplasty. Lower pole to upper pole pyeloureterostomy was necessary in four patients due to short ureteral length between the UPJ and junction of lower and upper pole ureters. No complications or obstruction of either moiety developed during 1 year of follow up.\n\nConclusions: Lower pole UPJO in incomplete renal duplication mandates individualized GSK1838705A mw surgical treatment

dependent upon anatomy encountered. We have found that pyeloureterostomy is a safe alternative to drainage of the obstructed lower pole. (C) 2009 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.”
“Bioenergy and energy crops are an important part of the UK’s renewable energy strategy to reach its greenhouse gas reduction target of 80% by 2050. Ensuring the sustainability of biomass feedstocks requires a greater understanding of all aspects of energy crop production, their ecological impacts and yields. This work compares the life-cycle environmental impact of natural gas and biomass from two energy crop systems grown P505-15 molecular weight under typical UK agronomic practice. As reported in previous studies the energy crops provide significant reductions in global warming potential (GWP) compared to natural gas. Compared to no fertiliser application, applying inorganic fertiliser increases the GWP by 2% and applying sewage sludge increases the GWP by a lesser extent. In terms of an equivalent GWP savings per unit area of land, the emissions associated with fertiliser production and application can be offset by a yield increase of <0.2 t/ha. However, very large increases in eutrophication and acidification levels are incurred compared to the natural gas reference case when applying either fertiliser.

We show that both oral and intratracheal TLR7 therapy can reduce the frequency of pulmonary metastasis, and metastasis

to the axillary lymph nodes. These results demonstrate that SM-276001 is a potent selective TLR7 agonist that can induce antitumor immune responses when dosed either intratracheally or orally.”
“The consumption of vegetables has been correlated with reduced risk of chronic non-communicable diseases due to the high fiber content and bioactive compounds found in vegetables. The arrowleaf elephant ear (Xanthosoma sagittifolium), which check details is known in Brazil as taioba, is a common plant in tropical America. Although its leafy portion possesses a high nutritional value, it is not widely consumed and has not been well studied. This study assessed the effect of lyophilised taioba leaf (LTL) as a hypolipidemic and prebiotic agent. Thirty-two Wistar rats were assigned to four groups: group 1 was fed a high-fat diet containing 3.67% (w/w) cellulose (low cellulose – LCEL); group 2 received a high-fat

diet supplemented with 10% (w/w) cellulose (CEL); group 3 received a high-fat diet supplemented with 10% (w/w) inulin (INU); and group 4 was fed a high-fat diet supplemented with 28.4% LTL (TAI) to provide 10% (w/w) taioba fiber. The groups were fed their respective diets for 4 weeks. The addition of LTL to the diet resulted in reduced weight gain, reduced liver fat, and increased Selleckchem CBL0137 fecal mass and lipid, in addition to higher fecal short chain fatty acid and bile salt concentrations, compared to the LCEL group. Additionally, only the TAI group exhibited a lower serum cholesterol concentration and a higher body ash content (p<0.05) than the LCEL group. Both the EX-527 high bile salt binding capacity and high fermentability of LTL suggest

that this plant may have a protective effect against cardiovascular diseases and bowel cancer. (C) 2013 Elsevier Ltd. All rights reserved.”
“Background. Small intestinal bacterial overgrowth (SIBO) is the excessive growth of nonpathogenic bacterial flora in the upper part of the small intestine. Its diagnosis is based on direct and indirect methods, such as the hydrogen breath test, which is widely used in children. Functional diseases of the gastrointestinal (GI) tract are among the most frequently diagnosed in children and they limit their daily activities. The symptoms of SIBO and lactose intolerance may be overlooked in patients with some functional diseases of the GI tract due to similar clinical symptoms. In contrast to functional diseases of the GI tract, SIBO may significantly disturb the digestion and absorption of food ingredients, leading to disturbances in physical development.\n\nObjectives. Assessment of the prevalence of SIBO in selected functional disorders of the GI system in children, i.e. functional dyspepsia and irritable bowel syndrome (IBS). Disturbance of lactose absorption and lactose intolerance were also assessed.\n\nMaterial and Methods.

“
“Pulmonary intravascular macrophages (PIMs) are present in species such as cattle, sheep and horse and promote acute lung inflammation (ALI). Rabbits are often used as a model of ALI but there is controversy about the presence of PIMs in these species. Rabbits were treated with 10 mg/kg of gadolinium chloride intravenously

(GC; n = 6) or saline (n = 6) followed by euthanasia at 48 h post-treatment to determine the presence of PIMs. In a subsequent study, rabbits were pre-treated with GC or 0.9 % saline followed by 100 mu g/kg of E. coli lipopolysaccharide intravenously 48 h later. Rabbits were euthanized 24 h post-LPS treatment. Light and electron microscopy showed that PIMs attached to the capillary endothelium and were positive Epigenetics inhibitor for RAM-11 anti-macrophage MEK inhibitor antibody. While GC treatment induced apoptotic PIMs, there was no difference in the PIM number between control

and GC-treated rabbits. Rabbits administered with LPS were 3.5 times more likely to die before the end of the 24-h period than those pre-treated with GC. Lung heterophil accumulation and IL-1 beta, TNF alpha and IL-6 mRNA expression were significantly higher in rabbits administered with LPS compared to those administered with GC before the LPS injection. PIMs from the LPS-treated rabbits were positive for TNF alpha. Lung, BAL and serum IL-8 and MCP-1 expression was not different between LPS rabbits with or without pre-treatment with GC. We conclude that rabbit lungs contain PIMs and that their depletion reduces endotoxin-induced lung inflammation. The presence of PIMs in rabbit lungs may need to be considered while using rabbit to model acute lung injury.”
“Attractive petals are an integral component of animal-pollinated

flowers and in many flowering plant species are restricted to the second floral whorl. Interestingly, multiple times during angiosperm evolution, petaloid characteristics Autophagy inhibitor mouse have expanded to adjacent floral whorls or to extra-floral organs. Here, we investigate developmental characteristics of petaloid sepals in Rhodochiton atrosanguineum, a close relative of the model species Antirrhinum majus (snapdragon). We undertook this in two ways, first using scanning electron microscopy we investigate the micromorphology of petals and sepals, followed by expression studies of genes usually responsible for the formation of petaloid structures. From our data, we conclude that R. atrosanguineum petaloid sepals lack micromorphological characteristics of petals and that petaloid sepals did not evolve through regulatory evolution of B-class MADS box genes, which have been shown to specify second whorl petal identity in a number of model flowering plant species including snapdragon. These data, in conjunction with other studies, suggests multiple convergent pathways for the evolution of showy sepals.

Strategies for selecting appropriate patients for mTOR inhibitor therapy and minimizing the risks of AEs are discussed, along with best practices for identifying and managing side effects. mTOR inhibitors are promising therapeutic options in immunosuppression and oncology; most AEs can be effectively detected and managed or reversed with careful monitoring and appropriate interventions. (C) 2014 The Authors. Published by Elsevier Inc.”
“Eye formation is regulated

by a complex network of eye field transcription factors (EFTFs), including buy PF-03084014 LIM-homeodomain gene LHX2. We disrupted LHX2 function at different stages during this process using a conditional knock-out strategy in mice. We find that LHX2 function is required in an ongoing fashion to maintain optic identity across multiple stages, from the formation of the optic vesicle to the differentiation of the neuroretina. At each stage, loss of Lhx2 led to upregulation of a set of molecular markers that are normally expressed in the thalamic eminence and in the anterodorsal hypothalamus in a portion of the optic vesicle or retina. Furthermore, the longer LHX2 function was maintained, the further optic morphogenesis progressed. Early loss of function

caused profound mispatterning of the entire telencephalic-optic-hypothalamic EPZ5676 field, such that the optic vesicle became mispositioned and appeared to arise from the diencephalic-telencephalic boundary. At subsequent stages, loss of Lhx2 did not affect optic vesicle position but caused arrest Ro-3306 supplier of optic cup formation. If Lhx2 was selectively disrupted in the neuroretina from E11.5, the neuroretina showed gross dysmorphology along with aberrant expression of markers specific to the thalamic eminence and anterodorsal hypothalamus. Our findings indicate a continual requirement for LHX2 throughout the early stages of optic development, not only to maintain optic identity by suppressing alternative fates but also to mediate multiple steps of optic morphogenesis. These findings provide new insight into the anophthalmic phenotype of the Lhx2 mutant and reveal novel roles for this transcription

factor in eye development.”
“We exploit the concept of competing interactions to design a binary mixture of patchy particles that forms a reversible gel upon heating. Our molecular dynamics computer simulation of such a system shows that with increasing temperature the relaxation dynamics slows down by more than four orders of magnitude and then speeds up again. The system is thus a fluid both at high and at low temperatures and a solid-like disordered open network structure at intermediate temperature. We further discuss the feasibility of realizing a real material with this reversible behavior.”
“The role of vasopressin (AVP) in the pathophysiology of cardiovascular disease is controversial, but this peptide hormone is elevated in heart failure and some forms of hypertension.