Evaluating the neurophysiological evidence for predictive processing as a model of perception

For many years, the dominant theoretical framework guiding research into the neural origins of perceptual experience has been provided by hierarchical feedforward models, in which sensory inputs are passed through a series of increasingly complex feature detectors. However, the long‐standing orthodoxy of these accounts has recently been challenged by a radically different set of theories that contend that perception arises from a purely inferential process supported by two distinct classes of neurons: those that transmit predictions about sensory states and those that signal sensory information that deviates from those predictions. Although these predictive processing (PP) models have become increasingly influential in cognitive neuroscience, they are also criticized for lacking the empirical support to justify their status. This limited evidence base partly reflects the considerable methodological challenges that are presented when trying to test the unique predictions of these models. However, a confluence of technological and theoretical advances has prompted a recent surge in human and nonhuman neurophysiological research seeking to fill this empirical gap. Here, we will review this new research and evaluate the degree to which its findings support the key claims of PP

Anticancer and Antifungal Activity of Copper(II) Complexes of Quinolin-2(1H)-one-Derived Schiff Bases

The condensation of substituted aromatic aldehydes with 7-amino-4-methyl-quinolin-2(1H)-one (1) has lead to the isolation of quinolin-2(1H)-one derived Schiff bases (2–14). The copper(II) complexes (2a–14a) of the ligands were also prepared, and together with their corresponding free ligands were fully characterised by elemental analyses, spectral methods (IR, 1H and 13C NMR, AAS, UV–Vis), magnetic and conductance measurements. The bidentate ligands coordinated to the copper(II) ion through the deprotonated phenolic oxygen and the azomethine nitrogen of the ligands in almost all cases. X-ray crystal structures of two of the complexes, 5a and 8a, confirmed the bidentate coordination mode. All of the compounds were investigated for their antimicrobial activities against the fungus, Candida albicans, and against Gram-positive and Gram-negative bacteria. The compounds were found to have excellent anti-Candida activity but were inactive against Staphylococcus aureus and Escherichia coli. Selected compounds (2–8 and 2a–8a) were also screened for their in vitro anticancer potential using the human hepatic carcinoma cell line, Hep-G2. Several derivatives were shown to be active comparable to that of cisplatin

Anticancer and antifungal activity of copper(II) complexes of quinolin-2(1H)-one-derived Schiff bases

The condensation of substituted aromatic aldehydes with 7-amino-4-methyl-quinolin-2(1H)-one (1) has lead to the isolation of quinolin-2(1H)-one derived Schiff bases (2–14). The copper(II) complexes (2a–14a) of the ligands were also prepared, and together with their corresponding free ligands were fully characterised by elemental analyses, spectral methods (IR, 1H and 13C NMR, AAS, UV–Vis), magnetic and conductance measurements. The bidentate ligands coordinated to the copper(II) ion through the deprotonated phenolic oxygen and the azomethine nitrogen of the ligands in almost all cases. X-ray crystal structures of two of the complexes, 5a and 8a, confirmed the bidentate coordination mode. All of the compounds were investigated for their antimicrobial activities against the fungus, Candida albicans, and against Gram-positive and Gram-negative bacteria. The compounds were found to have excellent anti-Candida activity but were inactive against Staphylococcus aureus and Escherichia coli. Selected compounds (2–8 and 2a–8a) were also screened for their in vitro anticancer potential using the human hepatic carcinoma cell line, Hep-G2. Several derivatives were shown to be active comparable to that of cisplatin

The influence of sarcoplasmic reticulum Ca2+ concentration on Ca2+ sparks and spontaneous transient outward currents in single smooth muscle cells

Localized, transient elevations in cytosolic Ca2+, known as Ca2+ sparks, caused by Ca2+ release from sarcoplasmic reticulum, are thought to trigger the opening of large conductance Ca2+-activated potassium channels in the plasma membrane resulting in spontaneous transient outward currents (STOCs) in smooth muscle cells. But the precise relationships between Ca2+ concentration within the sarcoplasmic reticulum and a Ca2+ spark and that between a Ca2+ spark and a STOC are not well defined or fully understood. To address these problems, we have employed two approaches using single patch-clamped smooth muscle cells freshly dissociated from toad stomach: a high speed, wide-field imaging system to simultaneously record Ca2+ sparks and STOCs, and a method to simultaneously measure free global Ca2+ concentration in the sarcoplasmic reticulum ([Ca2+]SR) and in the cytosol ([Ca2+]CYTO) along with STOCs. At a holding potential of 0 mV, cells displayed Ca2+ sparks and STOCs. Ca2+ sparks were associated with STOCs; the onset of the sparks coincided with the upstroke of STOCs, and both had approximately the same decay time. The mean increase in [Ca2+]CYTO at the time and location of the spark peak was approximately 100 nM above a resting concentration of approximately 100 nM. The frequency and amplitude of spontaneous Ca2+ sparks recorded at -80 mV were unchanged for a period of 10 min after removal of extracellular Ca2+ (nominally Ca2+-free solution with 50 microM EGTA), indicating that Ca2+ influx is not necessary for Ca2+sparks. A brief pulse of caffeine (20 mM) elicited a rapid decrease in [Ca2+]SR in association with a surge in [Ca2+]CYTO and a fusion of STOCs, followed by a fast restoration of [Ca2+]CYTO and a gradual recovery of [Ca2+]SR and STOCs. The return of global [Ca2+]CYTO to rest was an order of magnitude faster than the refilling of the sarcoplasmic reticulum with Ca2+. After the global [Ca2+]CYTO was fully restored, recovery of STOC frequency and amplitude were correlated with the level of [Ca2+]SR, even though the time for refilling varied greatly. STOC frequency did not recover substantially until the [Ca2+]SR was restored to 60% or more of resting levels. At [Ca2+]SR levels above 80% of rest, there was a steep relationship between [Ca2+]SR and STOC frequency. In contrast, the relationship between [Ca2+]SR and STOC amplitude was linear. The relationship between [Ca2+]SR and the frequency and amplitude was the same for Ca2+ sparks as it was for STOCs. The results of this study suggest that the regulation of [Ca2+]SR might provide one mechanism whereby agents could govern Ca2+ sparks and STOCs. The relationship between Ca2+ sparks and STOCs also implies a close association between a sarcoplasmic reticulum Ca2+ release site and the Ca2+-activated potassium channels responsible for a STOC

Recipient screening in IVF: First data from women undergoing anonymous oocyte donation in Dublin

BACKGROUND: Guidelines for safe gamete donation have emphasised donor screening, although none exist specifically for testing oocyte recipients. Pre-treatment assessment of anonymous donor oocyte IVF treatment in Ireland must comply with the European Union Tissues and Cells Directive (Directive 2004/23/EC). To determine the effectiveness of this Directive when applied to anonymous oocyte recipients in IVF, we reviewed data derived from selected screening tests performed in this clinical setting. METHODS: Data from tests conducted at baseline for all women enrolling as recipients (n = 225) in the anonymous oocyte donor IVF programme at an urban IVF referral centre during a 24-month period were analysed. Patient age at programme entry and clinical pregnancy rate were also tabulated. All recipients had at least one prior negative test for HIV, Hepatitis B/C, chlamydia, gonorrhoea and syphilis performed by her GP or other primary care provider before reproductive endocrinology consultation. RESULTS: Mean (±SD) age for donor egg IVF recipients was 40.7 ± 4.2 yrs. No baseline positive chlamydia, gonorrhoea or syphilis screening results were identified among recipients for anonymous oocyte donation IVF during the assessment interval. Mean pregnancy rate (per embryo transfer) in this group was 50.5%. CONCLUSION: When tests for HIV, Hepatitis B/C, chlamydia, gonorrhoea and syphilis already have been confirmed to be negative before starting the anonymous donor oocyte IVF sequence, additional (repeat) testing on the recipient contributes no new clinical information that would influence treatment in this setting. Patient safety does not appear to be enhanced by application of Directive 2004/23/EC to recipients of anonymous donor oocyte IVF treatment. Given the absence of evidence to quantify risk, this practice is difficult to justify when applied to this low-risk population

Role of cell cycle events and apoptosis in mediating the anti-cancer activity of a silver(I) complex of 4-hydroxy-3-nitro-coumarin-bis(phenanthroline) in human malignant cancer cells.

The central objective of the current study was to investigate the potential in vitro anti-proliferative effect of 4-hydroxy-3-nitro-coumarin (hncH), and the mixed-ligand silver (I) complex of 4-oxy-3-nitro-coumarin-bis (phenanthroline), [Ag(hnc)(phen)2] using four human-derived model cell lines. In addition, selected mechanistic studies were carried out using the most sensitive of the four cell lines. Results obtained show that the complex could decrease the proliferation of all four cell lines including neoplastic renal and hepatic, namely A-498 and HepG2 cells, respectively, along with two non-neoplastic renal and hepatic cell lines, HK-2 and Chang, respectively. Furthermore, non-neoplastic hepatic cells (Chang) appeared to be less sensitive to the effect of the complex, but this effect was not replicated in the non-neoplastic renal (HK-2) cells. Based on IC50 values [Ag(hnc)(phen)2] was shown to be almost four times more potent than cisplatin, using HepG2 cells. In addition, the observed anti-proliferative effect was shown to be both dose- and time-dependent. Furthermore, the complex was shown to decrease DNA synthesis, but did not intercalate with it. Moreover, there was no evidence that P-glycoprotein-mediated multi-drug resistance was likely to decrease antiproliferative activity. Cytological stains, analysis of genomic DNA, and biochemical assays [caspase-3 and -9 and cleaved poly(ADP-ribose)-polymerase protein] showed that cell death appeared to result from apoptosis, with the possibility of secondary necrosis. Additionally, flow cytometric analysis showed that the complex functioned through an alteration in cell cycle progression. Taken together, [Ag(hnc)(phen)2] has been shown to be a more potent anti-proliferative agent than cisplatin, capable of altering key biochemical events leading to cell death. Additional mechanistic studies are underway to probe more fully its mechanism of action

Sea level pressure response to the specification of eddy-resolving sea surface temperature in simulations of Australian east coast lows

Four east coast lows (ECLs) were simulated with the Weather Research and Forecast model to investigate the influence of the sea surface temperature (SST) distribution on the sea level pressure (SLP). Each ECL was simulated with two different SST datasets: the Bluelink SST field and NCEP skin temperature field. The former resolved eddies in the East Australian Current while the latter did not. The simulated SLP fields in the eddy-resolving SST runs were compared with those in the non-eddy-resolving SST runs. On time-scales of about 48 hours, higher SSTs were asso-ciated with lower SLPs. The spatial scale of the SLP response was similar to that of the ocean eddies, indicative of the rapidity and robustness of the response given the rapidly evolving conditions within the storms. On shorter time-scales, the SLP response to SST change can become substantially larger. The largest reductions in SLP in the eddy-resolving SST runs were associated with regions of deep atmospheric convection that warm the tropospheric column. These areas were shown to be related to the SST distribution with the greatest SLP reductions associated with convection over strong SST gradient regions. The landfall of a damaging convective mesoscale low pressure system on 8 June 2007 was also investigated. It was found that a region of strong SST gradients on the southern flank of a large warm ocean eddy was associated with lower pressures at the time of formation of this meso-low. In addition, the only case that simulated the low pressure at the correct time (albeit at not quite the correct location) was the eddy-resolved SST run. It was hy-pothesized that the development of this meso-low that impacted the coast around Newcastle, was enhanced because of the eddy-scale SST distribution at the time