These experiments suggest that cell factors are required for effi

These experiments suggest that cell factors are required for efficient reverse transcription of HIV-1.”
“Mice of the I/LnJ inbred strain are unique in their ability to mount a robust and sustained humoral immune response capable of neutralizing infection with a betaretrovirus, mouse mammary tumor virus (MMTV). Virus-neutralizing antibodies (Abs) coat MMTV virions secreted by infected cells, preventing virus spread

and hence the formation of mammary tumors. To investigate whether I/Lnj mice resist infection with other retroviruses besides MMTV, the animals were infected with murine leukemia virus (MuLV), a gammaretrovirus. MuLV-infected I/LnJ mice produced virus-neutralizing Abs that block virus transmission and vitally induced disease. Generation of virus-neutralizing Abs required gamma interferon but was independent of interieukin-12. This unique mechanism of retrovirus MEK162 supplier resistance is governed by a single recessive gene, virus infectivity controller 1 (vic1), mapped to chromosome 17. In addition to controlling

the antivirus humoral immune response, vic1 is also required for an antiviral cytotoxic response. Both types of responses were maintained in mice of the susceptible genetic background but congenic for the I/LnJ vic1 locus. Although the vic1-mediated resistance to MuLV resembles the mechanism of retroviral recovery controlled by the resistance selleck chemical to Friend virus 3 (rfv3) gene, the rfv3 gene has been mapped to chromosome 15 and confers resistance to MuLV but not to MMTV. Thus, we have identified a unique virus resistance mechanism that controls immunity against two distinct retroviruses.”
“A single blind, randomized, placebo-controlled, single-center phase I clinical trial of a CD8(+) T-cell peptide epitope vaccine against infectious mononucleosis

was conducted with 14 HLA B*0801-positive, LDC000067 clinical trial Epstein-Barr virus (EBV)-seronegative adults. The vaccine comprised the HLA B*0801-restricted peptide epitope FLRGR AYGL and tetanus toxoid formulated in a water-in-oil adjuvant, Montanide ISA 720. FLRGRAYGL-specific responses were detected in 8/9 peptide-vaccine recipients and 0/4 placebo vaccine recipients by gamma interferon enzyme-linked immunospot assay and/or limiting-dilution analysis. The same T-cell receptor V beta CDR3 sequence that is found in FLRGRAYGL-specific T cells from most EBV-seropositive individuals could also be detected in the peripheral blood of vaccine recipients. The vaccine was well tolerated, with the main side effect being mild to moderate injection site reactions. After a 2- to 12-year follow-up, 1/2 placebo vaccinees who acquired EBV developed infectious mononucleosis, whereas 4/4 vaccinees who acquired EBV after completing peptide vaccination seroconverted asymptomatically. Single-epitope vaccination did not predispose individuals to disease, nor did it significantly influence development of a normal repertoire of EBV-specific CD8(+) T-cell responses following seroconversion.

This consists of a short-latency response (SLR) corresponding

This consists of a short-latency response (SLR) corresponding

to the mono- and oligosynaptic reflex and a medium-latency response (MLR) relayed by group-II spindle afferent fibers and likely made of a segmental burst and a transcortical loop.

Soleus (Sol) SLR and MLR were evoked by toe-up and tibialis anterior (TA) MLR by toe-down platform rotation in 15 standing subjects and recorded by surface electromyogram (EMG). For each stimulus type, up to 20 perturbations were elicited during i) quiet stance (Control) and while ii) performing JM, iii) leaning forward (FW), iv) holding onto a stable frame (Holding). For each subject, stimulus type and condition, rectified EMG traces were averaged. Based on the comparison of the population PSI-7977 datasheet grand averages, selective effects of JM on the responses were identified. Appropriate time windows were set for measuring the area of SLR and of the early and late burst AZD1080 of MLR (MLR1 and MLR2).

Significant changes in response size, but not latency, were induced by all conditioning procedures. During toe-up, JM slightly increased Sol SLR; FW increased both Sol background activity and SLR; MLR1 was not affected by JIM, but increased by FW; MLR2 was

strongly diminished by JM and increased by FW. During toe-down, JM did not affect TA MLR1, but strongly diminished MLR2. Under Holding condition, Sol SLR to toe-up was unaffected, but both MLR1 and MLR2 to toe-up and toe-down were diminished, in both Sol and TA.

JM selectively decreases the response component (MLR2) starting about 100 ms from onset of the stretch, in both extensor and flexor muscles. Latency and quality of the JIM effect on MLR2 indicate that JM operates by gating a long-loop, possibly transcortical pathway. This new information suggests that lesions of cortical areas or descending pathways can exert enhancing effects on muscle tone by removing an inhibitory action on the late component

of the stretch reflex. (C) 2008 IBRO. CHIR99021 Published by Elsevier Ltd. All rights reserved.”
“Background: For good rehabilitation candidates, the biomechanical advantages of the end weight-bearing through-knee amputation (TKAmp) compared with the above knee amputation (ARA) are well established. However, the TKAmp has been abandoned by vascular surgeons because of poor wound healing rates related to long tissue flaps and challenges to prosthetic fitting related to the femoral condyles. Since 1998, we have performed the modified “”Mazet”" technique TKAmp procedure that creates shorter flaps to close the wound and greatly facilitates prosthesis fitting. The purpose of this study is to review our results with TKAmp in patients with peripheral vascular disease who were not candidates for below-knee amputation.

Methods: The records of all patients who underwent through-knee amputation between 1998 and 2006 were retrospectively reviewed. Mean follow-up was 33 months (range, 38 days to 99 months).

Strategies were statistically compared with the McNemar test

Strategies were statistically compared with the McNemar test.

Results: Mean +/- SD patient age was 63.3 +/- 7.2 years. Median prostate specific antigen was 6.7 ng/ml (IQR 4.7-10.0). Clinically significant cancer was detected by magnetic resonance imaging targeted biopsy and template guided prostate biopsy in 103 (57%) and 113 of the 182 men (62%) (p = 0.174), and clinically insignificant cancer was detected in 17 (9.3%) and 31 (17.0%), respectively (p = 0.024).

Conclusions: Prostate biopsy targeted to suspicious

lesions on multiparametric magnetic resonance imaging has encouraging rates of detection of clinically significant cancer while also decreasing the detection rate of clinically insignificant Pevonedistat manufacturer cancer. This is achieved with fewer biopsy cores than for systematic template guided biopsy. Further prospective, multicenter, comparative trials of the performance of targeting strategies are needed to consider magnetic resonance imaging targeted biopsy an alternative LY3023414 chemical structure to conventional systematic biopsy.”
“Purpose: We recently reported an increasing risk over time of hospitalization among Medicare participants after undergoing an initial prostate biopsy. Less is known about the relative risks of repeat prostate biopsies, which are frequently performed in prostate cancer screening and in see more active surveillance

programs. We determined whether repeat biopsies are associated with an increased risk of hospitalization compared to the initial biopsy.

Materials and Methods: Using SEER (Surveillance, Epidemiology and End Results)-Medicare linked data from 1991 to 2007 we identified 13,883 men who underwent a single prostate biopsy and 3,640 who had multiple biopsies. The 30-day hospitalization rates were compared between these groups, and with a randomly selected control population of 134,977. ICD-9 codes were then used to examine the frequency of serious infectious

and noninfectious urological complications as the primary diagnosis for hospital admissions.

Results: Initial and repeat biopsies were associated with a significantly increased risk of hospitalization within a 30-day period compared to randomly selected controls (p < 0.0001). However, the repeat biopsy session was not associated with a greater risk of infectious (OR 0.81, 95% 0.49-1.32, p = 0.39) or serious noninfectious urological complications (OR 0.94, 95% CI 0.54-1.62, p = 0.82) compared to the initial biopsy.

Conclusions: Each biopsy was associated with a significant risk of complications compared to randomly selected controls. However, the repeat biopsy procedure itself was not associated with a greater risk of serious complications requiring hospital admission compared to the initial biopsy.

Triptolide, a diterpene

triepoxide, is one of the major a

Triptolide, a diterpene

triepoxide, is one of the major active components of these extracts. To clarify its antiproteinuric effects we induced podocyte injury by puromycin aminonucleoside. Triptolide effectively reduced the proteinuria induced by puromycin in nephrotic rats without reducing the glomerular filtration rate. The antiproteinuric effect was associated with Ricolinostat mw improvement in the foot process effacement, a decrease in the podocyte injury marker desmin as well as the restoration of nephrin and podocin expression and distribution. In cultured mouse podocytes triptolide pretreatment prevented the puromycin-induced disruption of the actin cytoskeleton and microfilament-associated synaptopodin while protecting nephrin and podocin expression. Triptolide suppressed reactive oxygen species generation and p38 mitogen-activated protein kinase activation while restoring RhoA signaling activity. These results show that triptolide ameliorates puromycin aminonucleoside-mediated podocyte injury in vivo and in vitro.”
“Increased selleck chemical extra-hypothalamic corticotrophin-releasing factor (CRF) neurotransmission has been suggested as one putative factor in the pathophysiology of anxiety

disorders. We have previously reported that administering repeated subanxiogenic doses (termed ‘priming’) of the CRF receptor agonist urocortin 1 (Ucn1) into the basolateral amygdala (BLA) of rats elicited long-lasting behavioral changes in social interaction (SI) and elevated plus maze (EPM) tests of anxiety. Although substantial similarity exists, the bed nucleus of the stria terminals (BNST) and the amygdala are thought to play distinct roles in anxiety responses. Rats primed with Ucn1 in the BLA not only demonstrated increased anxiety-like behaviors, but also physiological sensitivity to intravenous sodium lactate infusions, which is seen in subjects with panic or posttraumatic stress disorders, but not social or generalized anxiety disorders. In the present study, we tested if similar priming with subanxiogenic doses of Ucn1 in the AZD6738 nmr BNST of rats will induce either chronic anxiety or sensitivity to sodium lactate. After determining the

dose of Ucn1 that is subanxiogenic when injected into the BNST, repeated intra-BNST injections of this subanxiogenic dose of Ucn1 (6 fmol/100 nl) elicited persistent (present even after 4 weeks) anxiety-like responses in the SI but not EPM test. Prior local injection of a CRF receptor antagonist, astressin, into the BNST blocked this effect. Unlike Ucn1 priming in the BLA, rats primed in the BNST showed no cardiovascular changes following lactate infusion. Thus, BNST priming appears to selectively model the pathophysiology of subjects with anxiety syndromes like social anxiety, which are not lactate sensitive.”
“A wealth of research identifies the amygdala as a key brain region mediating negative affect, and implicates amygdala dysfunction in the pathophysiology of anxiety disorders.

311), perceived income adequacy (-0 121), older age (-0 073 per y

311), perceived income adequacy (-0.121), older age (-0.073 per year), poor vision (-0.754), diabetes mellitus (-0.565), refusal to report household income (1.48), ever had Medicaid

insurance (-0.610), obesity (-0.437), hospitalization in the prior year (-0.521), and kidney disease (-.956).

Conclusions. The effect of baseline SPPB on adverse outcomes in this late middle-age African American population confirms reports involving older, primarily white participants. Alleviating deterioration in lower body physical functioning guided by the associated covariates may avoid or delay multiple age-associated adverse outcomes.”
“OBJECTIVE: We sought to investigate the three-dimensional structure of the white matter of the brain by means of the fiber-dissection technique and diffusion-tensor magnetic resonance imaging to assess the usefulness of the combination of both techniques, compare their results, and review Navitoclax the potential functional role of fiber tracts.

METHODS: Fifteen formalin-fixed human hemispheres were dissected according to Klingler’s fiber-dissection technique with the aid of X6 to X40 magnification. Three-dimensional anatomic images were created with the use of specific software. Two hundred patients with neurological symptoms and five healthy volunteers were find more studied with diffusion-tensor

magnetic resonance imaging (3 T) and tractographic reconstruction.

RESULTS: The most important association, projection, and commissural fasciculi were identified anatomically and radiologically. Analysis of their localization, configuration, and trajectory Fludarabine order was enhanced by the combination of both techniques. Three-dimensional anatomic reconstructions provided a

better perception of the spatial relationships among the white matter tracts. Tractographic reconstructions allowed for inspection of the relationships between the tracts as well as between the tracts and the intracerebral lesions. The combination of topographical anatomic studies of human fiber tracts and neuroanatomic research in experimental animals, with data from the clinicoradiological analysis of human white matter lesions and intraoperative subcortical stimulation, aided in establishing the potential functional role of the tracts.

CONCLUSION: The fiber-dissection and diffusion-tensor magnetic resonance imaging he techniques are reciprocally enriched not only in their application to the study of the complex intrinsic architecture of the brain, but also in their practical use for diagnosis and surgical planning.”
“Background. Both oral health problems and cognitive impairment are relatively common among older adults. Poorer oral health appears to contribute to a decline in quality of life and to be related to various medical conditions. Little is known about the relationship of cognitive function to oral health among community-dwelling older adults.

Methods.

Furthermore, increased endothelial-dependent microvessel relaxati

Furthermore, increased endothelial-dependent microvessel relaxation was observed in the coronary arteries

of VE-Cad/RTEF-1 mice, and increased proliferation was observed in RTEF-1-overexpressing cells, both of which correlated to increased FGF/FGFR1 signaling and endothelial nitric oxide synthase (eNOS) upregulation. Our results indicate that RTEF-1 acts as a transcriptional stimulator of FGFR1 and is involved in FGF pathways by increasing microvessel dilatation via eNOS. Conclusions: These findings suggest that RTEF-1 https://www.selleckchem.com/products/pf299804.html plays an important role in FGFR1-stimulated vasodilatation. Understanding the effect of RTEF-1 in microvessel relaxation may provide beneficial knowledge in improving treatments in regards to ischemic vascular disorders. Copyright (C) 2012 S. Karger AG, Basel”
“Nicotine has both rewarding and aversive properties in rodents, as shown by intravenous self-administration, intracranial self-stimulation, and conditioned place preference experiments. However, high throughput models of nicotine reward have not been developed in mice. In previous Fosbretabulin nmr two-bottle studies, mice often chose to drink less from the nicotine bottle than from the water bottle, which raises the question whether these paradigms provide a model of the reinforcing properties of oral nicotine. We hypothesized

that previous two-bottle choice paradigms included factors (such as the brief duration of trials, the addition of flavorings to both bottles, water bottles located relatively close to each other, etc.) that may have obstructed the formation of a learned association between the taste of nicotine and its delayed pharmacological effects. Here we show that a paradigm designed to simplify the acquisition of a learned association resulted

in nicotine consumption by various strains and sexes that diverged progressively over a period of seven weeks. The strain https://www.selleck.cn/products/tubastatin-a.html and sex with the highest nicotine consumption (C57BL/6J females) showed steady and statistically significant increases in nicotine consumption throughout this period. C57BL/6J females were clearly responding to the reinforcing properties of nicotine because they chose to drink over 70% of their fluids from the nicotine bottle. Moreover, they became nicotine dependent, as shown by highly significant nicotine withdrawal symptoms after the nicotine bottle was removed. The strain and sex with the lowest consumption (A/J males) showed a significant decrease in nicotine consumption, and by the end of the experiment were drinking only 24% of their fluids from the nicotine bottle. (C) 2012 Elsevier Ltd. All rights reserved.”
“Wnt/frizzled signaling in the adult heart is quiescent under normal conditions; however it is reactivated after myocardial infarction (MI). Any intervention at the various levels of this pathway can modulate its signaling.

Recombinant CHO cell lines expressing either tumor necrosis facto

Recombinant CHO cell lines expressing either tumor necrosis factor receptor as an Fc fusion protein (TNFR:Fc) or an anti-RhesusD monoclonal antibody were cultivated in the two systems. The 5-L OSR was operated in an incubator shaker with 5% CO(2) in the gas environment

but without pH and DO control whereas the STR was operated with or without pH and DO control. Higher cell densities and recombinant protein titers were obtained in the OSR as compared to both the controlled and the non-controlled STRs. To test the reproducibility of a bioprocess in a non-controlled OSR, Src inhibitor the two CHO cell lines were each cultivated in parallel in six 5-L OSRs. Similar cell densities, cell viabilities, and recombinant protein titers along with similar pH and DO profiles were achieved in each group of replicates. Our study demonstrated that bioprocesses can be performed in OSRs without pH or DO control in a highly reproducible manner, at least at the scale of operation

studied here.”
“The case of a 49-year-old male patient who presented with recurrent pulmonary emboli secondary to a calcified lesion within his inferior vena cava is presented. The diagnosis and relevant literature is reviewed. This is the first time that calcification within the inferior vena cava has presented this way in adults, and it is important to consider this diagnosis in patients presenting with recurrent pulmonary emboli. (J Vase Surg 2011;53:204-5.)”
“Methods of stabilization and formulation of proteins are important in both biopharmaceutical and biocatalysis industries. Polymers are often used as modifiers XMU-MP-1 of characteristics of biological macromolecules to improve the biochemical activity and

stability of proteins or drug bioavailability. Green fluorescent protein (GFP) shows remarkable structural Veliparib chemical structure stability and high fluorescence; its stability can be directly related to its fluorescence output, among other characteristics. GFP is stable under increasing temperatures, and its thermal denaturation is highly reproducible. Relative thermal stability was undertaken by incubation of GFP at varying temperatures and GFP fluorescence was used as a reporter for unfolding. At 80 degrees C, DEAE-dextran did not have any effect on GFP fluorescence, indicating that it does not confer stability.”
“Primary portal venous aneurysms are rare; however, they are the most common visceral venous aneurysms, and their pathogenesis is not fully understood. Complications include thrombosis, rupture, and mass effect on adjacent structures. The optimal management of these patients is not known. We describe a patient whose large (6-cm) portal vein aneurysm underwent complete spontaneous regression over several years of serial observation. To our knowledge, this observation has not been reported in the English literature. (J Vase Surg 2011;53:206-8.

Of 30 Kelly patients without urinary diversion 21 (70%) were comp

Of 30 Kelly patients without urinary diversion 21 (70%) were completely or partially continent. Of the 30 patients 17

voided spontaneously without clean intermittent catheterization or augmentation, of whom 12 (71%) were continent. Lower abdominal appearance was graded as abnormal in 11 of 12 male Kelly patients vs in 2 of 7 nonKelly males with pubic approximation (p=0.01). Of the 12 females assessed none of 9 Kelly selleck chemicals patients had prolapse, whereas 2 of 3 nonKelly patients had prolapse (p<0.05).

Conclusions: The continence rate after the Kelly operation compares favorably with that in recent series. The abnormal appearance of the lower abdomen and bony pelvis in Kelly males may result from a lack of pubic approximation. Importantly pelvic organ prolapse may be decreased in women after the Kelly technique.”
“BACKGROUND

It has been hypothesized that internal tocodynamometry, as compared with external monitoring, may provide a more accurate assessment of contractions and thus improve the ability to adjust the dose of oxytocin effectively, resulting in fewer operative deliveries and less fetal distress. However, few data are available to test this hypothesis.

METHODS

We performed a randomized, controlled trial in six hospitals in the Netherlands to compare internal tocodynamometry with external monitoring

of uterine activity in women for whom induced or augmented labor was required. The primary outcome was the rate of operative deliveries, including SBI-0206965 purchase both cesarean sections and instrumented vaginal deliveries. Secondary outcomes included the use of antibiotics during

labor, time from randomization to delivery, and adverse neonatal outcomes (defined as any of the following: an Apgar score at 5 minutes of less than 7, umbilical-artery pH of less than 7.05, and neonatal hospital stay of longer than 48 hours).

RESULTS

We randomly assigned 1456 women to either internal tocodynamometry (734) check details or external monitoring (722). The operative-delivery rate was 31.3% in the internal-tocodynamometry group and 29.6% in the external-monitoring group (relative risk with internal monitoring, 1.1; 95% confidence interval [CI], 0.91 to 1.2). Secondary outcomes did not differ significantly between the two groups. The rate of adverse neonatal outcomes was 14.3% with internal monitoring and 15.0% with external monitoring (relative risk, 0.95; 95% CI, 0.74 to 1.2). No serious adverse events associated with use of the intrauterine pressure catheter were reported.

CONCLUSIONS

Internal tocodynamometry during induced or augmented labor, as compared with external monitoring, did not significantly reduce the rate of operative deliveries or of adverse neonatal outcomes. (Current Controlled Trials number, ISRCTN13667534; Netherlands Trial number, NTR285.

Adenosine receptors are colocalized and functionally interact wit

Adenosine receptors are colocalized and functionally interact with dopamine receptors in the brain. Thus, functional polymorphisms in the Selleck 5-Fluoracil genes for either adenosine or dopamine receptors may affect responses to caffeine. In this study,

we examined associations between self-reported anxiogenic effects of caffeine and variation in the genes for A(2A) (ADORA2A) and DRD(2) (DRD(2)) receptors. Healthy male and female individuals (n = 102), who consumed less than 300 mg caffeine per week, ingested capsules containing 0, 50, 150, and 450 mg caffeine under double-blind conditions in four separate experimental sessions. Subjective anxiety was measured before and at repeated times selleck chemicals after capsules were consumed. At the

150 mg dose of caffeine, we found a significant association between caffeine-induced anxiety ( Visual Analog Scales, VAS) and ADORA2A rs5751876 (1976C/T), rs2298383 (intron 1a) and rs4822492 (3′-flank), and DRD2 rs1110976 (intron 6). Caffeine-induced anxiety (VAS) was also associated with two-loci interactions of selected ADORA2A and DRD2 polymorphisms. The lowest dose of caffeine did not increase ratings of anxiety while the highest dose increased anxiety in the majority of subjects. These findings provide support for an association between an ADORA2A polymorphism and self-reported anxiety after a moderate dose of caffeine. It is likely that other ADORA2A and DRD2 polymorphisms also contribute to responses to caffeine.”
“In traditional Kaplan-Meier or Cox regression analysis, usually a risk factor measured at baseline

is related to mortality thereafter. During Givinostat chemical structure follow-up, however, things may change: either the effect of a fixed baseline risk factor may vary over time, resulting in a weakening or strengthening of associations over time, or the risk factor itself may vary over time. In this paper, short-term versus long-term effects (so-called time-dependent effects) of a fixed baseline risk factor are addressed. An example is presented showing that underweight is a strong risk factor for mortality in dialysis patients, especially in the short run. In contrast, overweight is a risk factor for mortality, which is stronger in the long run than in the short run. In addition, the analysis of how time-varying risk factors (so-called time-dependent risk factors) are related to mortality is demonstrated by paying attention to the pitfall of adjusting for sequelae. The proper analysis of effects over time should be driven by a clear research question. Both kinds of research questions, that is those of time-dependent effects as well those of time-dependent risk factors, can be analyzed with time-dependent Cox regression analysis. It will be shown that using time-dependent risk factors usually implies focusing on short-term effects only.

Promising trends involve (a) studies where both functional and an

Promising trends involve (a) studies where both functional and anatomical connectivity data are collected using high-resolution neuroimaging methods and (b) the development of advanced quantitative models of integration.”
“Some of the earliest studies of retroviral integration targeting reported that sites of gammaretroviral DNA integration were positively correlated with DNase I-hypersensitive sites in chromatin. This led to the suggestion that open chromatin was favorable for integration. More recent deep sequencing experiments confirmed that gammaretroviral integration sites and

DNase I cleavage sites are associated in genome-wide surveys. Paradoxically, in vitro studies of integration show that nucleosomal DNA is actually favored over naked DNA, LY2090314 nmr raising the question of whether integration target DNA in chromosomes is wrapped in nucleosomes or nucleosome free. In this study we examined gammaretroviral integration by infecting primary human CD4(+) T lymphocytes with a murine leukemia virus (MLV)-based retroviral vector or xenotropic murine leukemia virus-related virus (XMRV), and isolated 32,585 unique integration sites using ligation-mediated AZD2281 ic50 PCR and 454 pyrosequencing. CD4(+) T lymphocytes were chosen for study because of the particularly

dense genome-wide mapping of chromatin features available for comparison. Analysis relative to predicted nucleosome positions showed that gammaretroviruses direct integration into outward-facing major grooves on nucleosome-wrapped DNA, similar to the integration pattern of HIV. Also, a suite of histone modifications correlated

with gene activity are positively associated with integration by both MLV and XMRV. Thus, we conclude that favored selleck integration near DNase I-hypersensitive sites does not imply that integration takes place exclusively in nucleosome-free regions.”
“The binding sites for agonists and antagonist of orexin receptors are not know, hampering progressive drug design approaches. In the current study, we utilized chimaeric orexin receptor approach to map the receptor areas contributing to the selectivity of the classical antagonist, SB-334867, for OX1 receptors. Altogether ten chimaeras between OX1 and OX2 orexin receptors were utilized. The receptors were transiently expressed in HEK-293 cells. The ability (K-B) of SB-334867 to inhibit orexin-A-induced inositol phosphate release (phospholipase C activity) was measured. The results, in synthesis, suggest that there are several possible interactions contributing to the high affinity binding, all of which are not required simultaneously. This is indicated by the fact that most of the chimaeras display affinity (at least somewhat) higher than OX2.