Inhibition of Cdk1 also

causes defects in the organizatio

Inhibition of Cdk1 also

causes defects in the organization of endocytic and exocytic zones at the site of growth. Cdk1 thus modulates membrane-trafficking dynamics, which is likely to play an important role in coordinating find protocol cell surface growth with cell cycle progression.”
“For more than two decades, the cheetah (Acinonyx jubatus) has been considered a paradigm of disease vulnerability associated with low genetic diversity, particularly at the immune genes of the major histocompatibility complex (MHC). Cheetahs have been used as a classic example in numerous conservation genetics textbooks as well as in many related scientific publications. However, earlier studies used methods with low resolution to quantify MHC diversity and/or small sample sizes. Furthermore, high disease susceptibility

was reported only for captive cheetahs, whereas free-ranging cheetahs show no signs of infectious diseases and a good general health status. We examined whether the diversity at MHC class I and class II-DRB loci in 149 Namibian cheetahs was higher than previously reported using single-strand conformation polymorphism analysis, cloning, and sequencing. MHC genes were examined at the genomic and transcriptomic levels. We detected ten MHC class I and four class II-DRB alleles, of which nine MHC class I and all class II-DRB alleles were expressed. Phylogenetic analyses and individual genotypes suggested that the alleles belong to four MHC class I and three class II-DRB putative HIF inhibitor loci. Evidence of positive selection was detected in both MHC loci. Our study indicated that the low number of MHC class I alleles previously observed in cheetahs was due to a smaller sample size examined. On the other hand, the low number of MHC class II-DRB alleles previously observed in cheetahs was further confirmed. Compared with other mammalian species including felids, cheetahs showed low levels of MHC diversity, but this does not seem to influence the immunocompetence of free-ranging

cheetahs in Namibia and contradicts the previous conclusion that the cheetah is a paradigm species of disease vulnerability.”
“The cytoplasmic tail of the influenza A virus M2 protein is required for the production MLN8237 Cell Cycle inhibitor of infectious virions. In this study, critical residues in the M2 cytoplasmic tail were identified by single-alanine scanning mutagenesis. The tyrosine residue at position 76, which is conserved in >99% of influenza virus strains sequenced to date, was identified as being critical for the formation of infectious virus particles using both reverse genetics and a protein trans-complementation assay. Recombinant viruses encoding M2 with the Y76A mutation demonstrated replication defects in MDCK cells as well as in primary differentiated airway epithelial cell cultures, defects in the formation of filamentous virus particles, and reduced packaging of nucleoprotein into virus particles.

We used stable isotope analyses to evaluate body size-dependent t

We used stable isotope analyses to evaluate body size-dependent trophic and habitat shifts in krill during the austral summer around the South Shetland Islands, Antarctica. We found evidence Alvocidib clinical trial for an asymmetric, ontogenetic niche expansion with adults of both sexes having higher and more variable delta N-15 values but consistent delta C-13 values in comparison with juveniles. This result suggests that while phytoplankton likely remains an important life-long resource, krill in our study area expand their dietary niche to include higher trophic food sources as body size increases. The broader dietary niches observed in adults may help buffer them from recent climate-driven shifts in phytoplankton communities that

negatively affect larval or juvenile krill that rely predominately

on autotrophic resources.”
“To investigate the differences between the effects of mesenchymal stem cells (MSCs) administered in the early and late phases of tumorigenesis, MSCs were isolated from bone marrow and colorectal tumors were produced by exposing 7-week-old F344 rats to 1,2-dimethylhydrazine and dextran sulfate sodium. We evaluated tumor number and volume (week 25), MSC localization, number of aberrant crypt foci (ACF), transforming growth factor (TGF)-beta 1 protein levels in the rectum after A-769662 clinical trial administration of MSCs (week 5 or 15), and the effects of MSC-conditioned medium on ACL15 cell proliferation. Administered MSCs labeled with PKH26 were observed in the rectum. Administered MSCs in the early phase (week 5) before tumor Selleckchem MLN2238 occurrence (week 12) significantly decreased tumor number and volume (1.5 vs 4 and 21 mm(3) vs 170 mm(3); p smaller than 0.01), but not administered MSCs in the late phase (week 15). Administered MSCs in the early phase reduced

ACF number on days 14 and 35 (1.9 vs 4.1 and 3.7 vs 7.3; p smaller than 0.01). Rectal TGF-beta 1 increased 1.3 fold on day 3, and MSC-conditioned medium containing TGF-beta 1 abundantly inhibited ACL15 cell proliferation. MSCs administered in the early phase but not late phase inhibited colorectal tumor development in a rat model.”
“Background. YKL-40 association with human disease has been the object of many years of investigation. beta-thalassemia patients are affected by hepatic siderosis, which determines a fibrotic process and tissue remodelling. Chitotriosidase has been found to be increased in thalassemic patients returning to normal in patients submitted to bone marrow transplantation. YKL-40 is associated with macrophage activation in liver and in other tissues. The aim of the study was to analyse the level of serum YKL-40 and plasma chitotriosidase activity of patients with beta-thalassemia to assess whether their expression correlates with liver disease and degree of liver siderosis. Methods. Expression of YKL-40 and chitotriosidase as a marker of inflammation in 69 thalassemic patients were evaluated.

(Fabaceae-Faboideae), all of which are considered weeds in certai

(Fabaceae-Faboideae), all of which are considered weeds in certain situations. For light and scanning electron microscopy studies, we fixed and processed buds, flowers and fruits, according to usual methods, at different stages of development. We observed that the sclerenchymatous endocarp is essential for dehiscence in legumes, as well as for fragmentation in loments. We also found that the presence of hook-shaped trichomes, sclereid nests in the mesocarp, septum, hypodermis and the

formation of false septa are essential to the diaspore dispersal of the species studied.”
“The dorsal lateral geniculate nucleus (dLGN) contains a retinotopic map where Selleckchem Autophagy inhibitor input from the two eyes map in register to provide a substrate for binocular vision. Ten-m3, a transmembrane protein, mediates homophilic interactions and has been implicated in the patterning of ipsilateral visual projections. Ease of access to early developmental stages in a marsupial wallaby has been used to manipulate levels of Ten-m3 during the development of retinogeniculate projections. In situ hybridisation showed a high dorsomedial to low ventrolateral gradient of Ten-m3 in the developing

dLGN, matching retinotopically with the previously reported high ventral to low dorsal retinal gradient. Overexpression of Ten-m3 in ventronasal but not dorsonasal retina resulted in an extension of ipsilateral projections beyond the normal binocular zone. These results demonstrate that Ten-m3 influences ipsilateral projections and support a role for it in binocular mapping. (C) 2014 Elsevier Ireland PFTα Ltd. AZD1208 in vivo All rights reserved.”
“Background: The significance of amyloid precursor protein (APP) and neuroinflammation in idiopathic normal pressure hydrocephalus (iNPH) and Alzheimer’s disease (AD) is unknown. Objective: To investigate the role of soluble APP (sAPP) and amyloid beta (Ab) isoforms, proinflammatory cytokines, and biomarkers of neuronal damage in the cerebrospinal fluid (CSF) in relation to brain biopsy Ab and hyperphosphorylated tau (HPt) findings. Methods: The study population comprised 102 patients with possible NPH with cortical brain biopsies, ventricular and

lumbar CSF samples, and DNA available. The final clinical diagnoses were: 53 iNPH (91% shunt-responders), 26 AD (10 mixed iNPH+AD), and 23 others. Biopsy samples were immunostained against Ab and HPt. CSF levels of AD-related biomarkers (Ab42, p-tau, total tau), non-AD-related Ab isoforms (Ab38, Ab40), sAPP isoforms (sAPPa, sAPPb), proinflammatory cytokines (several interleukins (IL), interferon-gamma, monocyte chemoattractant protein-1, tumor necrosis factor-alpha) and biomarkers of neuronal damage (neurofilament light and myelin basic protein) were measured. All patients were genotyped for APOE. Results: Lumbar CSF levels of sAPP alpha were lower (p smaller than 0.05) in patients with shunt-responsive iNPH compared to non-iNPH patients. sAPPb showed a similar trend (p = 0.06).

“In the title compound, (C6H16N)[Zn(C6H4N3)(3)](n), the Zn

“In the title compound, (C6H16N)[Zn(C6H4N3)(3)](n), the Zn-II atom has a distorted tetrahedral geometry defined by four N atoms from four benzotriazolate (BTA) ligands.

The compound is composed of extended polymeric chains in which two BTA N atoms bridge [Zn(BTA)(2)] fragments along [001]. Cations and anions are linked by N-H center dot center dot center dot N hydrogen-bond interactions along [010].”
“Since the introduction of propofol, several drugs and methods have been used to alleviate the pain on its injection. This study was designed to evaluate the effect of adding sevoflurane 3% during preoxygenation in alleviation of pain on propofol injection.\n\nIn this randomized single-blinded study, 100 patients were randomly allocated equally into five groups: sevoflurane-lidocaine-tourniquet (SLT), sevoflurane-lidocaine (SL), lidocaine-tourniquet

(LT), lidocaine (L), and sevoflurane GW4869 ic50 (S). Approximately 10 min before the induction of anesthesia, midazolam 1-2 mg was administered intravenously to all patients. All patients received fentanyl 1 A mu g/kg as pretreatment check details and a full induction dose of propofol. A blinded anesthesia nurse assessed pain and hand movements throughout the injection of propofol.\n\nIn the SLT group, all patients (100%) were pain free and had no hand movements. There was no significant difference in pain grade or in hand movements between the L and the S groups,

or between the SLT and the SL groups. However, significant differences were observed in pain grade between the SLT and the L groups as well as between the SLT and the S groups. In addition, a significant difference in hand movement was observed only between the SLT and the S groups.\n\nThe addition of 3% sevoflurane at the time of preoxygenation for 1 min along with routine use of lidocaine-tourniquet completely prevented pain upon Rabusertib inhibitor propofol injection, whereas sevoflurane by itself provided similar analgesia to premixed lidocaine with propofol.”
“Objectives. This article stresses the importance of exclusion of malignant tumors as a cause of temporomandibular joint disorder, which is usually caused by intra-articular or musculoligamental dysfunction without considering malignant tumors as a cause of such complaints.\n\nMethod and Results. Three patients were referred to us because of persistent and recurrent temporomandibular joint dysfunction. All patients were treated more than once through their general practitioner, ear nose and throat physician, or dental physician without significant improvement. After adequate clinical and radiological examination, malignant tumors were discovered as a cause of such complaints.\n\nConclusions. Patients with primary or secondary tumors could present with symptoms simulating temporomandibular joint disorder and will therefore be treated similarly.

Genotyping was performed in 199 subsequent kidney graft recipient

Genotyping was performed in 199 subsequent kidney graft recipients from deceased donors without induction therapy based on polymerase chain reaction method using sequence-specific primers for TNF-alpha (-308A/G), IL-10 (-1082A/G, -819T/C and -592A/C), IL-6 (-174G/C),

IFN-gamma (+874T/A) and TGF-beta 1 (in codons 10T/C GW786034 manufacturer and 25G/C). Genotypes were grouped according to the strength of cytokine expression. During a 5-year follow-up period, 14 patients died with functioning graft and 33 developed graft failure. The analysed polymorphisms were not associated with the incidence of DGF. The frequency of early episodes of AR was significantly associated only with TGF-beta 1 genotype. There was an association between -174G/C IL-6 gene polymorphism and the death-censored kidney graft survival. The risk of graft loss during 5-year follow-up period was greater by 57% for GG or GC (higher IL-6 production) than for CC carriers. None of the other analysed polymorphisms significantly influenced both patients selleck chemical and kidney graft survival, also in the analysis of the subgroup with human leucocyte antigen-DR mismatch. -174G/C IL-6 genotype of the kidney graft recipient could modulate the rate of graft excretory function deterioration and the risk of graft loss by influencing their constitutional

“Purpose: The accuracy of predicting conversion from early-stage age-related macular degeneration NU7026 in vitro (AMD) to the advanced stages of choroidal neovascularization (CNV) or geographic atrophy (GA) was evaluated to determine whether inclusion of clinically relevant genetic markers improved accuracy beyond prediction using phenotypic risk factors alone.\n\nDesign: Cohort study.\n\nParticipants: White, non-Hispanic subjects participating in the Age-Related Eye Disease Study (AREDS) sponsored by the National Eye Institute consented to provide a genetic specimen. Of 2415 DNA specimens available, 940 were from disease-free subjects and 1475 were from subjects with early

or intermediate AMD.\n\nMethods: DNA specimens from study subjects were genotyped for 14 single nucleotide polymorphisms (SNPs) in genes shown previously to associate with CNV: ARMS2, CFH, C3, C2, FB, CFHR4, CFHR5, and F13B. Clinical demographics and established disease associations, including age, sex, smoking status, body mass index (BMI), AREDS treatment category, and educational level, were evaluated. Four multivariate logistic models (phenotype; genotype; phenotype + genotype; and phenotype + genotype + demographic + environmental factors) were tested using 2 end points (CNV, GA). Models were fitted using Cox proportional hazards regression to use time-to-disease onset data.

“Context -The Q-Probes program is a peer-comparison qualit

“Context.-The Q-Probes program is a peer-comparison quality assurance service offered by the College of American Pathologists that was created in 1989. Objective.-To establish national benchmarks around a specific quality metric at a specific point in time in anatomic pathology (AP). Design.-Q-Probes are based on a voluntary subscription for an individual study. Hospital-based laboratories in the United States, Canada, and 16 other countries have participated. Approximately one-third of all Q-Probes studies address AP metrics. Each Q-Probes study has a primary Selleckchem HDAC inhibitor quality indicator and additional minor indicators. Results.-There

have been 52 AP Q-Probes studies addressing process-, outcome-, and structure-related quality assurance LY3039478 in vivo issues. These Q-Probes studies often represented the first standardized national benchmark for specific metrics in the disciplines of cytopathology, surgical pathology, and autopsy pathology, and as such have been cited more than 1700 times in peer-reviewed literature. The AP Q-Probes studies that have been repeated over time demonstrate improvement in laboratory performance across an international spectrum. Conclusions.-The Q-Probes program has produced important national benchmarks in AP, addressing preanalytic, analytic, and postanalytic factors in the disciplines of cytopathology, surgical pathology, and autopsy

pathology. Q-Probes study data have been published, cited, Selleckchem eFT-508 and used in the creation of laboratory accreditation standards

and other national guidelines.”
“The overexpression of macrophage migration inhibitory factor (MIF) has been identified in a variety of tumors and the investigation of its molecular mechanisms in tumor progression is a key topic of research. The present study aimed to investigate MIF as a potential marker for disease control or recurrence, and to assess the association between serum and salivary MIF and the clinicopathological characteristics of patients with oral squamous Cell carcinoma (OSCC). Serum and salivary samples were collected prior to and following the surgical treatment of 50 patients with OSCC. MIF concentrations were assessed by enzyme-linked immunosorbent assay and the adopted level of statistical significance was P smaller than 0.05. The results revealed that serum MIF concentrations were significantly reduced following tumor resection in OSCC patients. Furthermore, higher preoperative salivary MIF concentrations were observed in patients with larger tumors and in those who succumbed to the disease. In conclusion, high salivary and serological MIF concentrations were identified in patients with OSCC. Nevertheless, only serological MIF concentrations may be considered as a potential marker for the early detection of OSCC recurrence once the salivary levels, prior and following treatment, do not show any significant differences.

The GFEM solution of a functionally graded thin rotating annular

The GFEM solution of a functionally graded thin rotating annular disk has been compared with the published literature and it shows good agreement.”
“A selective kanamycin-binding single-strand DNA (ssDNA) aptamer (TGGGGGTTGAGGCTAAGCCGA) was discovered through in vitro selection using affinity chromatography with kanamycin-immobilized sepharose beads. The selected Y-27632 mechanism of action aptamer has a high affinity for kanamycin and also for kanamycin derivatives such as kanamycin B and tobramycin. The dissociation constants (K(d) [kanamycin] = 78.8 nM, K(d) [kanamycin B] = 84.5 nM, and K(d) [tobramycin] = 103 nM) of the new aptamer were determined

by fluorescence intensity analysis using 5′-fluorescein amidite (FAM) modification. Using this aptamer, kanamycin was detected

down to 25 nM by the gold nanoparticle-based colorimetric method. Because the designed colorimetric method is simple, easy, and visible to the naked eye, it has advantages that AZD9291 research buy make it useful for the detection of kanamycin. Furthermore, the selected new aptamer has many potential applications as a bioprobe for the detection of kanamycin, kanamycin B, and tobramycin in pharmaceutical preparations and food products. (C) 2011 Elsevier Inc. All rights reserved.”
“Background: The inability to store fearful memories into their original encoding context is considered to be an important vulnerability factor for the development of anxiety disorders like posttraumatic stress disorder. Altered memory contextualization most likely involves effects of the stress hormone cortisol, acting via receptors located in the memory neurocircuitry. Cortisol via these receptors

induces rapid nongenomic effects followed by slower genomic effects, which are thought to modulate cognitive function in opposite, complementary ways. Here, we targeted these time-dependent effects of cortisol during memory encoding and tested subsequent IWR-1-endo solubility dmso contextualization of emotional and neutral memories.\n\nMethods: In a double-blind, placebo-controlled design, 64 men were randomly assigned to one of three groups: 1) received 10 mg hydrocortisone 30 minutes (rapid cortisol effects) before a memory encoding task; 2) received 10 mg hydrocortisone 210 minutes (slow cortisol) before a memory encoding task; or 3) received placebo at both times. During encoding, participants were presented with neutral and emotional words in unique background pictures. Approximately 24 hours later, context dependency of their memories was assessed.\n\nResults: Recognition data revealed that cortisol’s rapid effects impair emotional memory contextualization, while cortisol’s slow effects enhance it. Neutral memory contextualization remained unaltered by cortisol, irrespective of the timing of the drug.

ROS can alter chromosomal DNA, leading to genomic instability, an

ROS can alter chromosomal DNA, leading to genomic instability, and may serve as signaling molecules that affect tumor cell proliferation, survival, metabolism, angiogenesis, and metastasis. Targeting Noxs and

their downstream signaling components may be a promising approach to pre-empting inflammation-related malignancies. Published by Elsevier Ireland Ltd.”
“Background: From 1998 to 2008, 1000 skeletally mature patients underwent, autologous chondrocyte implantation for an osteochondral defect of the knee. We evaluated the functional outcomes in 827 of 869 patients who had undergone autologous chondrocyte implantation with Chondron or periosteum (ACI-C/ACI-P) or matrix-assisted PFTα chondrocyte implantation (MACI) and attempted to identify factors that influenced outcome. Methods: The age of the patient, the size and site of the osteochondral lesion, previous surgery, and the presence of early osteoarthritis were assessed for their influence on outcomes. Each factor was evaluated in a separate Cox proportional hazards model with use of hazard ratios (HRs), Vadimezan with 95% confidence intervals (CIs), describing the likelihood of failure for that particular factor. Outcomes were assessed with use of the modified Cincinnati score, visual analog scale pain score, and Stanmore functional score. Results: The mean duration of follow-up was 6.2 years (range, two to twelve years). The mean age

BEZ235 supplier was thirty-four years (range, fourteen to fifty-six years), with 493 males and 334 females. The average size of the defect was 409 mm(2) (range, 64 to 2075 mm2). Four hundred and twenty-one procedures (51%) were performed on the medial femoral condyle; 109 (13%), on the lateral femoral condyle; 200 (24%), on the patella; and fifty (6%), on the trochlea. Kaplan-Meier survival analysis revealed that the unadjusted graft survival rate was 78.2% at five years and 50.7% and ten years for the entire cohort. No difference was

found between the survival rates of the ACI-C/ACI-P and MACI techniques (HR = 0.948, 95% CI = 0.738 to 1.219, p = 0.678). There was a significant postoperative improvement in the function and pain scores of all three outcome measures (p smaller than 0.002). Survivorship in the group with a previous cartilage regenerative procedure was inferior to that in patients with a previously untreated lesion, with failure five times more likely in the former group (HR = 4.718, standard error [SE] = 0.742, 95% CI = 3.466 to 6.420, p smaller than 0.001). Degenerative change in any compartment had a significant detrimental effect on survivorship, with survivorship worsening as the osteoarthritis grade increased (Grade 1: HR = 2.077, 95% Cl = 1.299 to 3.322, p = 0.002; Grade 2: HR = 3.450, 95% CI = 2.646 to 4.498, p smaller than 0.001; and Grade 3: HR = 3.820, 95% Cl = 2.185 to 6.677, p smaller than 0.001).

aureus Transcriptional analyses showed that both indole and 7BOI

aureus. Transcriptional analyses showed that both indole and 7BOI repressed the expressions of several virulence genes such as alpha-hemolysin gene hla, enterotoxin seb, and the protease genes splA and sspA and modulated

the expressions Navitoclax inhibitor of the important regulatory genes agrA and sarA. These findings show that indole derivatives are potential candidates for use in antivirulence strategies against persistent S. aureus infection.”
“Flow cytometry is an effective tool for enumerating fluorescently-labeled microbes recovered from natural environments. However, low signal strength and the presence of fluorescent, non-cellular particles complicate the separation of cellular events from noise. Existing classification methods rely on the arbitrary placement

of noise thresholds, resulting in potentially high rates of misclassification of fluorescent cells, thus precluding the robust estimation of the proportions of classes of fluorescent cells. Here we present a method for objectively separating signal from noise. Rather than setting an arbitrary noise threshold, the Z-scoring approach uses the Gaussian distribution of signal strength (a) to locate noise threshold for individual fluorophores, (b) to predict the likelihood of different fluorescent genotypes in producing the signal CH5183284 mouse observed, and (c) to normalize the fraction of cellular events count for each fluorescent cell class.

The likelihood framework allows rejection of alternative genotypes, leading to robust and reliable classification of fluorescent cells. Use of Z-scoring in classification of cells expressing multiple fluorophores, use of spillover in actively scoring events, buy Cilengitide and the successful classification of multiple fluorophores using a single detector within a flow cytometer are discussed. A software package that performs Z-scoring for cells labeled with one or more fluorophores is described. (C) 2013 Elsevier B.V. All rights reserved.”
“Bio-nanocapsules (BNCs) consisting of hepatitis B virus (HBV) surface antigen (HBsAg) are approximately 50-nm hollow particles displaying a human hepatocyte-recognizing molecule (pre-S1 peptide). They have been used as an HB vaccine for the last two decades. Original BNC can incorporate various payloads (e.g., drugs, genes) by electroporation and deliver them to human hepatocytes specifically by utilizing the HBV infection mechanism. Here, we developed a new BNC conjugated with liposomes and succeeded in incorporating large materials (100-nm fluorescence-labeled polystyrene beads and > 30 kbp plasmids) into the BNC-liposome complex. The complex delivered these large materials to human hepatocytes specifically ex vivo and in vivo. The transfection efficiency of the BNC-liposome complex was significantly higher than that of the original BNC.

Based on the graph theory and Razumikhin technique, some conditio

Based on the graph theory and Razumikhin technique, some conditions are captured to guarantee that SFDEN is p-th moment and almost sure exponentially stable. Furthermore, the criterion selleck chemicals ensuring the exponential stability for stochastic coupled systems on networks with time-varying delay is established, by applying Razumikhin-type theorem. Finally, a numerical example is provided to demonstrate the

effectiveness of the theoretical results. (C) 2013 Elsevier B.V. All rights reserved.”
“A 10-year-old female spayed German Shepherd dog, with a year-long history of recurrent left ear infections, was presented for progressive ataxia, head tilt, and pain on opening of the mouth. On physical examination, a large amount of ceruminous debris was present in the left ear and multiple neurologic defects localizing to the cerebellum and vestibular system were identified. Magnetic resonance imaging (MRI) demonstrated a minimally contrast-enhancing mass within the left bulla, an intracranial space-occupying, heterogeneously contrast-enhancing lesion at the buy AZD7762 level of the left cerebello-medullary junction, and contrast enhancement of the ipsilateral meninges. Cerebrospinal fluid analysis revealed a marked mixed cell pleocytosis (nucleated cell count

655cells/L). The mass was visualized within the horizontal ear canal by otoscopic examination and a biopsy was taken. Impression smears of the biopsy contained many anucleate keratinized squamous epithelial cells, mild mixed inflammation, and few presumptive fibroblasts. With the provided clinical history and MRI findings, a cytologic diagnosis of cholesteatoma was made. A ventral bulla osteotomy was performed, and histopathologic examination of resected tissue confirmed the cytologic diagnosis of cholesteatoma. The dog’s clinical symptoms improved postoperatively, but the dog died of unrelated causes, 3.5months later. To our knowledge, this is the first description of the cytologic

features of a cholesteatoma, which is a nonneoplastic, but locally invasive epidermoid cyst, in the middle ear of dogs.”
“Urotensin II (U-II) is a disulfide bridged peptide hormone identified as the ligand of a G-protein-coupled receptor. Caspase inhibitor Human U-II (H-Glu-Thr-Pro-Asp-c[Cys-Phe-Trp-Lys-Tyr-Cys]-Val-OH) has been described as the most potent vasoconstrictor compound identified to date. We have recently identified both a superagonist of human U-II termed P5U (H-Asp-c[Pen-Phe-Trp-Lys-Tyr-Cys]-Val-OH) and the compound termed urantide (H-Asp-c[Pen-Phe-d-Trp-Orn-Tyr-Cys]-Val-OH), which is the most potent UT receptor peptide antagonist described to date. In the present study, we have synthesized four analogues of P5U and urantide in which the Trp7 residue was replaced by the highly constrained l-Tpi and d-Tpi residues. The replacement of the Trp7 by Tpi led to active analogues. Solution NMR analysis allowed improving the knowledge on conformationactivity relationships previously reported on UT receptor ligands.