Changes in lymphocyte subsets, interleukin 2, and soluble interleukin 2 receptor in old and very old age

In this study, the changes in some of the cellular components of the immune system and the activity of the cytokine interleukin 2, important for immune activation and lymphocyte proliferation, were measured in a large cross-sectional study of all age groups including octogenarian and nonagenarian subjects. In 206 apparently well community-living subjects, the absolute lymphocyte count and T and B cell numbers fell a little in old and very old subjects. Within the T cell compartment, helper/inducer CD4+ T cells, together with their subsets identified as 'naive' (CD4+/CD45RA+) and 'memory' (CD4+/CD45RO+) cells, also showed a decline with increased age. The suppressor/cytotoxic CD8+ subset showed no age-related change. The levels of the cytokine interleukin 2 were very low in octogenarian and nonagenarian subjects, while the soluble interleukin 2 receptor levels increased with increasing age. The interleukin 2 levels were associated with number and percentage of the 'memory' (CD4+/CD45RO+) subset of T cells which mediates the host response to previously met antigens. Since the interleukin 2 values were very low in the oldest groups and were associated with a reduced 'memory' (CD4+/CD45RO+) compartment, this suggests a possible mechanism of why the very elderly subject is more susceptible to morbidity and mortality from infectious or other agents.

Brucella abortus and its closest phylogenetic relative, Ochrobactrum spp., differ in outer membrane permeability and cationic peptide resistance

The outer membrane (OM) of the intracellular parasite Brucella abortus is permeable to hydrophobic probes and resistant to destabilization by polycationic peptides and EDTA. The significance of these unusual properties was investigated in a comparative study with the opportunistic pathogens of the genus Ochrobactrum, the closest known Brucella relative. Ochrobactrum spp. OMs were impermeable to hydrophobic probes and sensitive to polymyxin B but resistant to EDTA. These properties were traced to lipopolysaccharide (LPS) because (i) insertion of B. abortus LPS, but not of Escherichia coli LPS, into Ochrobactrum OM increased its permeability; (ii) permeability and polymyxin B binding measured with LPS aggregates paralleled the results with live bacteria; and (iii) the predicted intermediate results were obtained with B. abortus-Ochrobactrum anthropi and E. coli-O. anthropi LPS hybrid aggregates. Although Ochrobactrum was sensitive to polymyxin, self-promoted uptake and bacterial lysis occurred without OM morphological changes, suggesting an unusual OM structural rigidity. Ochrobactrum and B. abortus LPSs showed no differences in phosphate, qualitative fatty acid composition, or acyl chain fluidity. However, Ochrobactrum LPS, but not B. abortus LPS, contained galacturonic acid. B. abortus and Ochrobactrum smooth LPS aggregates had similar size and zeta potential (-12 to -15 mV). Upon saturation with polymyxin, zeta potential became positive (1 mV) for Ochrobactrum smooth LPS while remaining negative (-5 mV) for B. abortus smooth LPS, suggesting hindered access to inner targets. These results show that although Ochrobactrum and Brucella share a basic OM pattern, subtle modifications in LPS core cause markedly different OM properties, possibly reflecting the adaptive evolution of B. abortus to pathogenicity.

Explaining effervescence:: Shared social identity and positive experience in crowds

We develop and test a dual pathway model of effervescence - the intensely positive experience of being in a crowd. The model proposes that positive feelings arise when those attending a mass event see each other as sharing a common social identity. This sense of shared identity predicts (a) crowd participants’ ability to enact their valued collective identity, and (b) the intimacy of social relations between crowd members. In turn, both of these are theorized to predict crowd members’ positivity of experience. These ideas are tested using survey data from pilgrims (n = 416) attending the Magh Mela - a month-long Hindu pilgrimage festival in north India. The findings provide clear support for the model.

Invariant Information Local Sub-map Filter (IILSF) for Efficient Simultaneous Localisation and Mapping of Large Environments

This paper presents an Invariant Information Local Sub-map Filter (IILSF) as a technique for consistent Simultaneous Localisation and Mapping (SLAM) in a large environment. It harnesses the benefits of sub-map technique to improve the consistency and efficiency of Extended Kalman Filter (EKF) based SLAM. The IILSF makes use of invariant information obtained from estimated locations of features in independent sub-maps, instead of incorporating every observation directly into the global map. Then the global map is updated at regular intervals. Applying this technique to the EKF based SLAM algorithm: (a) reduces the computational complexity of maintaining the global map estimates and (b) simplifies transformation complexities and data association ambiguities usually experienced in fusing sub-maps together. Simulation results show that the method was able to accurately fuse local map observations to generate an efficient and consistent global map, in addition to significantly reducing computational cost and data association ambiguities.

A Probe-Goal Approach to Agreement and Incorporation Restrictions in Southern Tiwa

Southern Tiwa (Tanoan) exhibits agreement with up to three arguments (ergative, absolutive, dative). This agreement is subject to certain restrictions resembling the Person-Case Constraint paradigm (Bonet 1991). Moreover, there is a correlation between agreement restrictions and conditions on (the obviation of) noun-incorporation in Southern Tiwa, as explicitly and elegantly captured by Rosen (1990) in terms of a heterogeneous feature hierarchy and rules of association. We attempt to recast Rosen’s central insights in terms of Anagnostopoulou’s probe-sharing model of Person-Case Constraint effects (Anagnostopoulou 2003, 2006), to show that the full range of Southern Tiwa agreement and (non-)incorporation restrictions can be given a single, unified analysis within the probe-goal-Agree framework of Chomsky (2001). In particular, we argue that Southern Tiwa’s triple-agreement system is characterized by (a) an independent class probe located on the heads T and v, and (b) a rule that allows this class probe to be deleted in the context of local-person T-agreement. The various restrictions on agreement and non-incorporation then reduce to a single source: failure of class-valuation with DP (as opposed to NP) arguments.

Τesting models for the beginnings of the Aurignacian and the advent of figurative art and music: The radiocarbon chronology of Geißenklösterle

The German site of Geißenklösterle is crucial to debates concerning the European Middle to Upper Palaeolithic transition and the origins of the Aurignacian in Europe. Previous dates from the site are<br/>central to an important hypothesis, the Kulturpumpe model, which posits that the Swabian Jura was an area where crucial behavioural developments took place and then spread to other parts of Europe. The previous chronology (critical to the model), is based mainly on radiocarbon dating, but remains poorly constrained due to the dating resolution and the variability of dates. The cause of these problems is disputed, but two principal explanations have been proposed: a) larger than expected variations in the production of atmospheric radiocarbon, and b) taphonomic in?uences in the site mixing the bones that were dated into different parts of the site. We reinvestigate the chronology using a new series of radiocarbon determinations obtained from the Mousterian, Aurignacian and Gravettian levels. The results strongly imply that the previous dates were affected by insuf?cient decontamination of the bone collagen prior to dating. Using an ultra?ltration protocol the chronometric picture becomes much clearer. Comparison of the results against other recently dated sites in other parts of Europe suggests the Early Aurignacian levels are earlier than other sites in the south of France and Italy, but not as early as recently dated sites which suggest a pre-Aurignacian dispersal of modern humans to Italy byw45000 cal BP. They are consistent with the importance of the Danube Corridor as a key route for the movement of people and ideas. The new dates fail to refute the Kulturpumpe model and suggest that Swabian Jura is a region that contributed signi?cantly to the evolution of symbolic behaviour as indicated by early evidence for ?gurative art, music and mythical imagery. © 2012 Elsevier Ltd. All rights reserved.

Landfill cap models under simulated climate change precipitation::Impacts of cracks and root growth

Desiccation crack formation is a key process that needs to be understood in assessment of landfill cap performance under anticipated future climate change scenarios. The objectives of this study were to examine: (a) desiccation cracks and impacts that roots may have on their formation and resealing, and (b) their impacts on hydraulic conductivity under anticipated climate change precipitation scenarios. Visual observations, image analysis of thin sections and hydraulic conductivity tests were carried out on cores collected from two large-scale laboratory trial landfill cap models (∼80 × 80 × 90 cm) during a year of four simulated seasonal precipitation events. Extensive root growth in the topsoil increased percolation of water into the subsurface, and after droughts, roots grew deep into low-permeability layers through major cracks which impeded their resealing. At the end of 1 year, larger cracks had lost resealing ability and one single, large, vertical crack made the climate change precipitation model cap inefficient. Even though the normal precipitation model had developed desiccation cracks, its integrity was preserved better than the climate change precipitation model.

Ranakinestatin-PPF from the Skin Secretion of the Fukien Gold-Striped Pond Frog, Pelophylax plancyi fukienensis: A Prototype of a Novel Class of Bradykinin Bb>2b> Receptor Antagonist Peptide from Ranid Frogs

The defensive skin secretions of many amphibians are a rich source of bradykinins and bradykinin-related peptides (BRPs). Members of this peptide group are also common components of reptile and arthropod venoms due to their multiple biological functions that include induction of pain, effects on many smooth muscle types, and lowering systemic blood pressure. While most BRPs are bradykinin receptor agonists, some have curiously been found to be exquisite antagonists, such as the maximakinin gene-related peptide, kinestatin—a specific bradykinin Bb>2b>-receptor antagonist from the skin of the giant fire-bellied toad, Bombina maxima. Here, we describe the identification, structural and functional characterization of a heptadecapeptide (DYTIRTRLHQGLSRKIV), named ranakinestatin-PPF, from the skin of the Chinese ranid frog, Pelophylax plancyi fukienensis, representing a prototype of a novel class of bradykinin Bb>2b>-receptor specific antagonist. Using a preconstricted preparation of rat tail arterial smooth muscle, a single dose of 10⁻⁶ M of the peptide effectively inhibited the dose-dependent relaxation effect of bradykinin between 10⁻¹¹ M and 10⁻⁵ M and subsequently, this effect was pharmacologically-characterized using specific bradykinin Bb>1b>- (desArg-HOE140) and Bb>2b>-receptor (HOE140) antagonists; the data from which demonstrated that the antagonism of the novel peptide was mediated through Bb>2b>-receptors. Ranakinestatin—PPF—thus represents a prototype of an amphibian skin peptide family that functions as a bradykinin Bb>2b>-receptor antagonist herein demonstrated using mammalian vascular smooth muscle.

Combined Analysis of Gamma-H2AX/53BP1 Foci and Caspase Activation in Lymphocyte Subsets Detects Recent and More Remote Radiation Exposures

Analysis of gamma-H2AX foci in blood lymphocytes is a promising approach for rapid dose estimation to support patient triage after a radiation accident but has one major drawback: the rapid decline of foci levels post-exposure cause major uncertainties in situations where the exact timing between exposure and blood sampling is unknown. To address this issue, radiation-induced apoptosis (RIA) in lymphocytes was investigated using fluorogenic inhibitors of caspases (FLICA) as an independent biomarker for radiation exposure, which may complement the gamma-H2AX assay. Ex vivo X-irradiated peripheral blood lymphocytes from 17 volunteers showed dose-and time-dependent increases in radiation-induced apoptosis over the first 3 days after exposure, albeit with considerable interindividual variation. Comparison with gamma-H2AX and 53BP1 foci counts suggested an inverse correlation between numbers of residual foci and radiation-induced apoptosis in lymphocytes at 24 h postirradiation (P = 0.007). In T-helper (CD4), T-cytotoxic (CD8) and B-cells (CD19), some significant differences in radiation induced DSBs or apoptosis were observed, however no correlation between foci and apoptosis in lymphocyte subsets was observed at 24 h postirradiation. While gamma-H2AX and 53BP1 foci were rapidly induced and then repaired after exposure, radiation-induced apoptosis did not become apparent until 24 h after exposure. Data from six volunteers with different ex vivo doses and post-exposure times were used to test the capability of the combined assay. Results show that simultaneous analysis of gamma-H2AX and radiation-induced apoptosis may provide a rapid and more accurate triage tool in situations where the delay between exposure and blood sampling is unknown compared to gamma-H2AX alone. This combined approach may improve the accuracy of dose estimations in cases where blood sampling is performed days after the radiation exposure. 

Optimizing the efficiency of the sub-map technique for large-scale simultaneous localization and mapping

A technique for optimizing the efficiency of the sub-map method for large-scale simultaneous localization and mapping (SLAM) is proposed. It optimizes the benefits of the sub-map technique to improve the accuracy and consistency of an extended Kalman filter (EKF)-based SLAM. Error models were developed and engaged to investigate some of the outstanding issues in employing the sub-map technique in SLAM. Such issues include the size (distance) of an optimal sub-map, the acceptable error effect caused by the process noise covariance on the predictions and estimations made within a sub-map, when to terminate an existing sub-map and start a new one and the magnitude of the process noise covariance that could produce such an effect. Numerical results obtained from the study and an error-correcting process were engaged to optimize the accuracy and convergence of the Invariant Information Local Sub-map Filter previously proposed. Applying this technique to the EKF-based SLAM algorithm (a) reduces the computational burden of maintaining the global map estimates and (b) simplifies transformation complexities and data association ambiguities usually experienced in fusing sub-maps together. A Monte Carlo analysis of the system is presented as a means of demonstrating the consistency and efficacy of the proposed technique.

Burkholderia cepacia complex epidemiology in persons with cystic fibrosis from Australia and New Zealand

The Burkholderia cepacia complex (Bcc) is a group of significant opportunistic respiratory pathogens which affect people with cystic fibrosis. In this study, we sought to ascertain the epidemiology and geographic species distribution of 116 Bcc isolates collected from people with CF in Australia and New Zealand. We performed a combination of recA-based PCR, amplified rDNA restriction analysis (ARDRA), pulsed-field gel electrophoresis and repetitive extragenic palindromic PCR on each isolate. Each Burkholderia cenocepacia isolate was also screened by PCR for the presence of the B. cepacia epidemic strain marker. One hundred and fourteen isolates were assigned to a species using recA-based PCR and ARDRA. B. cenocepacia, B. multivorans and B. cepacia accounted for 45.7%, 29.3% and 11.2% of the isolates, respectively. Strain analysis of B. cenocepacia revealed that 85.3% of the isolates were unrelated. One related B. cenocepacia strain was identified amongst 15 people. Whilst full details of person-to-person contact was not available, all patients attended CF centres in Queensland (Qld) and New South Wales (NSW). Although person-to-person transmission of B. cenocepacia strains has occurred in Australia, the majority of CF-related Bcc infections in Australia and New Zealand are most likely acquired from the environment.

Biotransformation of zearalenone and zearalenols to their major glucuronide metabolites reduces estrogenic activity

Zearalenone (ZEN) is a mycotoxin produced by Fusarium fungi. Once ingested, ZEN may be absorbed andmetabolised to a- and b-zearalenol (a-ZOL, b-ZOL), and to a lesser extent a- and b-zearalanol (a-ZAL,b-ZAL). Further biotransformation to glucuronide conjugates also occurs to facilitate the elimination ofthese toxins from the body. Unlike ZEN and its metabolites, information regarding the estrogenic activityof these glucuronide conjugates in various tissues is lacking. ZEN-14-O-glucuronide, a-ZOL-14-O-glucuronide,a-ZOL-7-O-glucuronide, b-ZOL-14-O-glucuronide and b-ZOL-16-O-glucuronide, previouslyobtained as the major products from preparative enzymatic synthesis, were investigated for their potentialto cause endocrine disruption through interference with estrogen receptor transcriptional activity.All five glucuronide conjugates showed a very weak agonist response in an estrogen responsive reportergene assay (RGA), with activity ranging from 0.0001% to 0.01% of that of 17b-estradiol, and also lessthan that of ZEN, a-ZOL and b-ZOL which have previously shown estrogenic potencies of the order 17bestradiol> a-ZOL > ZEN > b-ZOL. Confirmatory mass spectrometry revealed that any activity observedwas likely a result of minor deconjugation of the glucuronide moiety. This study confirms that formationof ZEN and ZOL glucuronides is a detoxification reaction with regard to estrogenicity, serving as a potentialhost defence mechanism against ZEN-induced estrogenic activity.

Early-type stars observed in the ESO UVES Paranal observatory project - IV. studies of CN, CH+ and CH in the interstellar medium

High spectral resolution (~80 000) and signal-to-noise observations from the Ultraviolet and Visual Echelle Spectrograph Paranal Observatory Project (UVES-POP) are used to study the interstellarmolecular lines CN (3874 Å), CH⁺ (3957, 4232 Å) and CH (3886, 4300 Å) towards 74 O- and B-type stellar sightlines. Additionally, archive data are presented for 140 ELODIE early-type stellar sightlines at R = 42 000, plus 25 FEROS at R = 48 000 and 3 UVES at R > 50 000, mainly in the CH⁺ (4232 Å) and CH (3886, 4300 Å) transitions. Detection rates are ~45 per cent for CN and ~67 per cent for the other lines in the POP sample, and ~10-15 per cent for CH⁺ and CH lines in the additional sample. CH and CH⁺ are well correlated between log[N(CH) cm^-2]~12-14, implying that these clouds are CH⁺-like CH and not CN-like CH. CH is also very well correlated with Na I D in the range log[N(Na I cm^-2]) ~12.2-14.2. A few sightlines show tentative velocity shifts of ~2 km s^-1 between CH and CH⁺, which appear to be caused by differences in component strength in blends, and hence do not provide firm evidence for shocks. Finally, we describe a search for ¹³CH⁺ in a sightline towards HD 76341. No ¹³CH⁺ is detected, placing a limit on the ¹³CH⁺ to ¹²CH⁺ ratio of ~0.01. If a formal fit is attempted, the equivalent width ratio in the two isotopes is a factor ~90 but with large errors. 

Relationships between Religion and Two Forms of Homonegativity in Europe—A Multilevel Analysis of Effects of Believing, Belonging and Religious Practice

This paper examines relationships between religion and two forms of homonegativity<br/>across 43 European countries using a bivariate response binary logistic multilevel model. The model analyzes effects of religious believing, belonging and practice on two response variables: a) a moral rejection of homosexuality as a practice and b) intolerance toward homosexuals as a group. The findings indicate that both forms of homonegativity are prevalent in Europe. Traditional doctrinal religious believing (belief in a personal God) is positively related to a moral rejection of homosexuality but to a much lesser extent associated with intolerance toward homosexuals as a group. Members of religious denominations are more likely than non-members to reject homosexuality as morally wrong and to reject homosexuals as neighbors. The analysis found significant differences between denominations that are likely context-dependent. Attendance at religious services is positively related to homonegativity in a majority of countries. The findings vary considerably across countries: Religion is more strongly related to homonegativity in Western than in Eastern Europe. In the post-soviet countries homonegativity appears to be largely a secular phenomenon. National contexts of high religiosity, high perceived government corruption, high income inequality and shortcomings in the implementation of gay rights in the countries’ legislations are statistically related to higher levels of both moralistic homonegativity and intolerance toward homosexuals as a group.

The microtubule targeting agent PBOX-15 inhibits integrin-mediated cell adhesion and induces apoptosis in acute lymphoblastic leukaemia cells

Although recent decades have seen an improved cure rate for newly diagnosed paediatric acute lymphoplastic leukaemia (ALL), the treatment options for adult ALL, T-cell ALL (T-ALL) and relapsed disease remain poor. We have developed a novel series of pyrrolo-1,5-benzoxazepine (PBOX) compounds and established their anticancer efficacy in a variety of human tumour cell types. Here, we demonstrate that PBOX-15 inhibits cell growth, and induces G2/M cell cycle arrest and apoptosis in both T-ALL and B-cell ALL (B-ALL) cells. In addition, prior to PBOX-15-induced apoptosis, PBOX-15 decreases ALL cell adhesion, spreading and migration. Concurrently, PBOX-15 differentially down-regulates β1-, β2- and α4-integrin expression in ALL cells and significantly decreases integrin-mediated cell attachment. PBOX-15 interferes with the lateral mobility and clustering of integrins in both B-ALL and T-ALL cells. These data suggest that PBOX-15 is not only effective in inducing apoptosis in ALL cells, but also has the potential to disrupt integrin-mediated adhesion of malignant lymphocytes, which represents a novel avenue for regulating leukaemic cell homing and migration.