Proteasome inhibitor-based therapy for antibody-mediated rejection

The development of donor-specific anti-human leukocyte antigen antibodies (DSAs) following renal transplantation significantly reduces long-term renal graft function and survival. The traditional therapies for antibody-mediated rejection (AMR) have provided inconsistent results and transient effects that may be due to a failure to deplete mature antibody-producing plasma cells. Proteasome inhibition (PI) is a novel AMR therapy that deletes plasma cells. Initial reports of PI-based AMR treatment in refractory rejection demonstrated the ability of bortezomib to deplete plasma cells producing DSA, reduce DSA levels, provide histological improvement or resolution, and improve renal allograft function. These results have subsequently been confirmed in a multicenter collaborative study. PI has also been shown to provide effective primary AMR therapy in case reports. Recent studies have demonstrated that PI therapy results in differential responses in early and late post-transplant AMR. Additional randomized studies are evaluating the role of PI in transplant induction, acute AMR, and chronic rejection in renal transplantation. An important theoretical advantage of PI-based regimens is derived from several potential strategies for achievement of synergy

Preliminary investigation of the influence of dopamine regulating genes on social working memory

Working memory (WM) refers to mental processes that enable temporary retention and manipulation of information, including information about other people (“social working memory”). Previous studies have demonstrated that nonsocial WM is supported by dopamine neurotransmission. Here, we investigated in 131 healthy adults whether dopamine is similarly involved in social WM by testing whether social and nonsocial WM are influenced by genetic variants in three genes coding for molecules regulating the availability of dopamine in the brain: catechol-O-methyltransferase (COMT), dopamine active transporter (DAT), and monoamine-oxidase A (MAOA). An advantage for the Met allele of COMT was observed in the two standard WM tasks and in the social WM task. However, the influence of COMT on social WM performance was not accounted for by its influence on either standard WM paradigms. There was no main effect of DAT1 or MAOA, but a significant COMT x DAT1 interaction on social WM performance. This study provides novel preliminary evidence of effects of genetic variants of the dopamine neurotransmitter system on social cognition. The results further suggest that the effects observed on standard WM do not explain the genetic effects on effortful social cognition

Spatial working memory is enhanced in children by differential outcomes

Working memory (WM) is essential to academic achievement. Any enhancement of WM abilities may improve children's school performance. We tested the usefulness of the differential outcomes procedure (DOP) to enhance typically developing children's performance on a spatial WM task. The DOP involves a conditional discriminative learning task in which a correct choice response to a specific stimulus-stimulus association is reinforced with a particular reinforcer (outcome). We adapted a spatial memory task to be used with the DOP. Participants had to learn and retain in their WM four target locations of eight possible locations where a shape could be presented. Two groups of 5- and 7-year-old children performed the low-attentional version of the spatial task, and an additional group of 7-year-old children performed the high-attentional version. The results showed that compared with the standard non-differential outcomes procedure (NOP), the DOP produced better memory-based performance in 5-year-old children with the low-attentional task and in 7-year-old children with the high-attentional task. Additionally, delay intervals impaired performance in the NOP but not in the DOP. These findings suggest that the DOP may be a useful complement to other WM intervention programs targeted to improve children's academic performance at school

Alkali extraction of archaeological and geological charcoal: evidence for diagenetic degradation and formation of humic acids

Charcoal forms a crucial source of archaeological and palaeoenvironmental data, providing a record of cultural activities, past climatic conditions and a means of chronological control via radiocarbon (<sup>14</sup>C) dating. Key to this is the perceived resistance of charcoal to post-depositional alteration, however recent research has highlighted the possibility for alteration and degradation of charcoal in the environment. An important aspect of such diagenesis is the potential for addition of exogenous 'humic acids' (HAs), to affect the accuracy of archaeological and palaeoenvironmental reconstructions based upon chemical analyses of HA-containing charcoal. However the release of significant quantities of HA from apparently pristine charcoals raises the question whether some HA could be derived via diagenetic alteration of charcoal itself. Here we address this question through comparison of freshly produced charcoal with samples from archaeological and geological sites exposed to environmental conditions for millennia using elemental (C/H/O) and isotopic (δ<sup>13</sup>C) measurements, Fourier Transform Infrared Spectroscopy (FTIR) and proton Liquid-State Nuclear Magnetic Resonance (<sup>1</sup>H NMR). The results of analyses show that the presence of highly carboxylated and aromatic alkali-extractable HA in charcoal from depositional environments can often be attributable to the effects of post-depositional processes, and that these substances can represent the products of post-depositional diagenetic alteration in charcoal

The independent group looks at London's west end

In the early 1950s, British culture was dominated by welfare-state visions of urban reconstruction. These projections of a stable civic society were premised on a particular way of looking at and reading the metropolitan environment. At odds with this project, the Independent Group's discussions and collaborative work developed an alternative urban semiology, which found the city to be already rich in visual resources for fashioning a more profound form of social democracy. Soon, this critical engagement would develop in different directions, represented here by Lawrence Alloway's commentary on Piccadilly Circus in his essay 'City Notes' and the London footage inserted by John McHale into his film for the Smithsons' Berlin Hauptstadt project (both 1959). By the end of the 1950s, members of the erstwhile Independent Group had produced two contrasting critical accounts of how the metropolitan centre should be looked at, which challenged the strictures of post-war reconstruction in distinct and conflicting ways. © The Author(s), 2013

Radiocarbon Dating of Wood Using Different Pretreatment Procedures: Application to the Chronology of Rotoehu Ash, New Zealand

We compare radiocarbon accelerator mass spectrometry (AMS) ages of wood samples subjected to a conventional acid-base-acid pretreatment with stepped combustion (ABA-SC) with results from the same samples subjected to an acid-base-wet oxidation pretreatment with stepped combustion (ABOX-SC) and cellulose extraction with stepped combustion (CE-SC). The ABOX-SC procedure has been shown previously to lead to lower backgrounds for old charcoal samples. Analyses of relatively uncontaminated" C-14-dead" samples of wood suggest that backgrounds of 0.11 +/- 0.04 pMC are obtainable for both the ABOX-SC and ABA-SC procedures. Where wood is significantly contaminated the ABOX-SC technique provides significantly better decontamination than either the ABA-SC technique or cellulose extraction alone, although CE-SC can produce comparably low backgrounds to the ABOX-SC procedure. We also report the application of the ABOX-SC, ABA-SC and CE-SC procedures to wood samples associated with the chronologically controversial Rotoehu Ash eruption, New Zealand. New C-14-AMS dates from wood sampled from below the Rotoehu Ash span an age range of 43-50 ka BP consistent with recently presented OSL dates of 42-44, ka obtained for palaeosols beneath the ash

Foliar lead uptake by lettuce exposed to atmospheric fallouts

Metal uptake by plants occurs by soil−root transfer but also by direct transfer of contaminants from the atmosphere to the shoots. This second pathway may be particularly important in kitchen gardens near industrial plants. The mechanisms of foliar uptake of lead by lettuce (Lactuca sativa) exposed to the atmospheric fallouts of a lead-recycling plant were studied. After 43 days of exposure, the thoroughly washed leaves contained 335 ± 50 mg Pb kg−1 (dry weight). Micro-X-ray fluorescence mappings evidenced Pb-rich spots of a few hundreds of micrometers in diameter located in necrotic zones. These spots were more abundant at the base of the central nervure. Environmental scanning electron microscopy coupled with energy dispersive X-ray microanalysis showed that smaller particles (a few micrometers in diameter) were also present in other regions of the leaves, often located beneath the leaf surface. In addition, submicrometric particles were observed inside stomatal openings. Raman microspectrometry analyses of the leaves identified smelter-originated Pb minerals but also secondary phases likely resulting from the weathering of original particles. On the basis of these observations, several pathways for foliar lead uptake are discussed. A better understanding of these mechanisms may be of interest for risk assessment of population exposure to atmospheric metal contamination

The effect of motor load on planning and inhibition in developmental coordination disorder

Previous research has reported mixed findings regarding executive function (EF) abilities in developmental coordination disorder (DCD), which is diagnosed on the basis of significant impairments in motor skills. The current study aimed to assess whether these differences in study outcomes could result from the relative motor loads of the tasks used to assess EF in DCD. Children with DCD had significant difficulties on measures of inhibition and planning compared to a control group, although there were no significant correlations between motor skills and EF task performance in either group. The complexity of the response, as well as the component skills required in EF tasks, should be considered in future research to ensure easier comparison across studies and a better understanding of EF in DCD over development

Synergistic activity between primary visual neurons

Abstract : Cortical microcircuitry plays a pivotal role in encoding sensory information reaching the cortex. However, the fundamental knowledge concerning the mechanisms that govern feature-encoding by these sub-networks is still sparse. Here, we show through multi electrode recordings in V1 of conventionally prepared anesthetized cats, that an avalanche of synergistic neural activity occurs between functionally connected neurons in a cell assembly in response to the presented stimulus. The results specifically show that once the reference neuron spikes in a connected neuron-pair, it facilitates the response of its companion (target) neuron for 50 ms and, thereafter, the excitability of the target neuron declines. On the other hand, the functionally unconnected neurons do not facilitate each other’s activity within the 50 ms time-window. The added excitation (facilitation) of connected neurons is almost four times the responsiveness of unconnected neurons. This suggests that connectedness confers the added excitability to neurons; consequently leading to feature-encoding within the emergent 50 ms-period. Furthermore, the facilitation significantly decreases as a function of orientation selectivity spread