Brain mechanisms of successful recognition through retrieval of semantic context

Episodic memory is associated with the encoding and retrieval of context information and with a subjective sense of reexperiencing past events. The neural correlates of episodic retrieval have been extensively studied using fMRI, leading to the identification of a "general recollection network" including medial temporal, parietal, and prefrontal regions. However, in these studies, it is difficult to disentangle the effects of context retrieval from recollection. In this study, we used fMRI to determine the extent to which the recruitment of regions in the recollection network is contingent on context reinstatement. Participants were scanned during a cued recognition test for target words from encoded sentences. Studied target words were preceded by either a cue word studied in the same sentence (thus congruent with encoding context) or a cue word studied in a different sentence (thus incongruent with encoding context). Converging fMRI results from independently defined ROIs and whole-brain analysis showed regional specificity in the recollection network. Activity in hippocampus and parahippocampal cortex was specifically increased during successful retrieval following congruent context cues, whereas parietal and prefrontal components of the general recollection network were associated with confident retrieval irrespective of contextual congruency. Our findings implicate medial temporal regions in the retrieval of semantic context, contributing to, but dissociable from, recollective experience

The integrated optic RF spectrum analyzer

The results of measurements made on a fully integrated optic RF spectrum analyzer (IOSA) are reported. The performance of the device acousto-optic bandwidth, single-tone RF resolution, two-tone RF resolution, single-tone dynamic range, two-tone dynamic range, and single-tone RF response are presented. The device parameters that control device performance are analyzed. These results demonstrate the viability of the IOSA for real time spectrum analysis of pulsed and CW RF signals. Improvements of RF bandwidth resolution can be obtained by the use of larger collimated optical beams which requires larger optical lens elements, and hence, larger crystals

Fatal acute haemolysis and methaemoglobinaemia in a man with renal failure and Alkaptonuria - Is nitisinone the solution?

Haemolysis and methaemoglobinaemia (MetHb) are rare metabolic complications that can occur in Alkaptonuria (AKU), for which there is no curative treatment. Presented is a case of a man who had AKU, and serves as a reminder of life-threatening complications that can occur with haemolysis and MetHb. This case presents an opportunity to revisit important considerations relating to the investigation and treatment of haemolysis and MetHb with a view to raising awareness, and in doing so hopefully reducing the uniformly fatal outcome. Additionally it is proposed that treatment of haemolysis and MetHb with nitisinone is considered as a potentially lifesaving treatment as it is believed that reducing the concentration of circulating homogentisic acid will reduce oxidative stress

Impact of schizophrenia on anterior and posterior hippocampus during memory for complex scenes.

ObjectivesHippocampal dysfunction has been proposed as a mechanism for memory deficits in schizophrenia. Available evidence suggests that the anterior and posterior hippocampus could be differentially affected. Accordingly, we used fMRI to test the hypothesis that activity in posterior hippocampus is disproportionately reduced in schizophrenia, particularly during spatial memory retrieval.Methods26 healthy participants and 24 patients with schizophrenia from the UC Davis Early Psychosis Program were studied while fMRI was acquired on a 3 Tesla Siemens scanner. During encoding, participants were oriented to critical items through questions about item features (e.g., "Does the lamp have a square shade?") or spatial location (e.g., "Is the lamp on the table next to the couch?"). At test, participants determined whether scenes were changed or unchanged. fMRI analyses contrasted activation in a priori regions of interest (ROI) in anterior and posterior hippocampus during correct recognition of item changes and spatial changes.ResultsAs predicted, patients with schizophrenia exhibited reduced activation in the posterior hippocampus during detection of spatial changes but not during detection of item changes. Unexpectedly, patients exhibited increased activation of anterior hippocampus during detection of item changes. Whole brain analyses revealed reduced fronto-parietal and striatal activation in patients for spatial but not for item change trials.ConclusionsResults suggest a gradient of hippocampal dysfunction in which posterior hippocampus - which is necessary for processing fine-grained spatial relationships - is underactive, and anterior hippocampus - which may process context more globally - is overactive

Length-dependent changes in contractile dynamics are blunted due to cardiac myosin binding protein-C ablation

Enhanced cardiac contractile function with increased sarcomere length (SL) is, in part, mediated by a decrease in the radial distance between myosin heads and actin. The radial disposition of myosin heads relative to actin is modulated by cardiac myosin binding protein-C (cMyBP-C), suggesting that cMyBP-C contributes to the length-dependent activation (LDA) in the myocardium. However, the precise roles of cMyBP-C in modulating cardiac LDA are unclear. To determine the impact of cMyBP-C on LDA, we measured isometric force, myofilament Ca2+-sensitivity (pCa50) and length-dependent changes in kinetic parameters of cross-bridge (XB) relaxation (krel), and recruitment (kdf) due to rapid stretch, as well as the rate of force redevelopment (ktr) in response to a large slack-restretch maneuver in skinned ventricular multicellular preparations isolated from the hearts of wild-type (WT) and cMyBP-C knockout (KO) mice, at SL’s 1.9µm or 2.1µm. Our results show that maximal force was not significantly different between KO and WT preparations but length-dependent increase in pCa50 was attenuated in the KO preparations. pCa50 was not significantly different between WT and KO preparations at long SL (5.82±0.02 in WT vs. 5.87±0.02 in KO), whereas pCa50 was significantly different between WT and KO preparations at short SL (5.71±0.02 in WT vs. 5.80±0.01 in KO; p<0.05). The ktr, measured at half-maximal Ca2+-activation, was significantly accelerated at short SL in WT preparations (8.74±0.56s-1at 1.9µm vs. 5.71±0.40s-1at 2.1µm, p<0.05). Furthermore, krel and kdf were accelerated by 32% and 50%, respectively at short SL in WT preparations. In contrast, ktr was not altered by changes in SL in KO preparations (8.03±0.54s-1at 1.9µm vs. 8.90±0.37s-1at 2.1µm). Similarly, KO preparations did not exhibit length-dependent changes in krel and kdf. Collectively, our data implicate cMyBP-C is an important regulator of LDA via its impact on dynamic XB behavior due to changes in SL

Remission in Rheumatoid Arthritis

With advancing therapeutic options, achieving a state of remission has become the treatment goal in rheumatoid arthritis. Agreeing on what constitutes remission and what measures should be used to assess disease activity has remained a challenge. Multiple remission criteria have been devised and modified, all with different strengths and limitations. A consensus definition of remission will need to be achieved if we are to be able to evaluate outcomes of clinical trials and establish treatment targets for practice. Remission defined as the complete absence of disease currently may not be a realistic therapeutic goal

Post-translational Regulation of Expression and Conformation of an Immunoglobulin Domain in Yeast Surface Display

Display of heterologous proteins on the surface of Saccharomyces cerevisiae is increasingly being exploited for directed evolution because of straightforward cell screens. However, yeast post-translationally modifies proteins in ways that must be factored into library engineering and refinement. Here, we express the extracellular immunoglobulin domain of an ubiquitous mammalian membrane protein, CD47, which is implicated in cancer, immunocompatibility, and motility. CD47 has multiple sites of glycosylation and a core disulfide bond. We assess the effects of both of these post-translational modifications on expression and antibody binding. CD47’s extracellular domain is fused to the yeast mating protein Aga2p on the cell wall, and the resulting fusion protein binds several key antibodies, including a conformation-sensitive antibody. Site-by-site mutagenesis of CD47’s five N-linked glycosylation sites progressively decreases expression levels on yeast, but folding appears stable. Cysteine mutations disrupt the expected core disulfide, and also decrease protein expression levels, though not to the extent seen with complete deglycosylation. However, with the core disulfide mutants, antibody binding proves to be lower than expression levels might indicate and glycosylation is clearly reduced compared to wild-type. The results indicate that glycosylation regulates heterologous display on yeast more than core disulfides do and thus suggest bounds on directed evolution by post-translational processing

Theta phase synchronization between the human hippocampus and prefrontal cortex increases during encoding of unexpected information: A case study

Events that violate predictions are thought to not only modulate activity within the hippocampus and PFC but also enhance communication between the two regions. Scalp and intracranial EEG studies have shown that oscillations in the theta frequency band are enhanced during processing of contextually unexpected information. Some theories suggest that the hippocampus and PFC interact during processing of unexpected events, and it is possible that theta oscillations may mediate these interactions. Here, we had the rare opportunity to conduct simultaneous electrophysiological recordings from the human hippocampus and PFC from two patients undergoing presurgical evaluation for pharmacoresistant epilepsy. Recordings were conducted during a task that involved encoding of contextually expected and unexpected visual stimuli. Across both patients, hippocampal–prefrontal theta phase synchronization was significantly higher during encoding of contextually unexpected study items, relative to contextually expected study items. Furthermore, the hippocampal–prefrontal theta phase synchronization was larger for contextually unexpected items that were later remembered compared with later forgotten items. Moreover, we did not find increased theta synchronization between the PFC and rhinal cortex, suggesting that the observed effects were specific to prefrontal–hippocampal interactions. Our findings are consistent with the idea that theta oscillations orchestrate communication between the hippocampus and PFC in support of enhanced encoding of contextually deviant information

Impaired recollection of visual scene details in adults with autism spectrum conditions.

Subtle memory deficits observed in autism spectrum conditions (ASC) have often been characterized as reflecting impaired recollection and it has been proposed that a relational binding deficit may underlie the recollection impairment. However, subjective recollection and relational binding have not been measured within the same task in ASC to date and it is unclear whether a relational binding deficit can provide a full account of recollection impairments in ASC. Relational memory has also not been compared with item memory when the demands of the 2 tasks are comparable. To assess recollection, relational memory, and item memory within a single task in ASC, 24 adults with ASC and 24 typically developed adults undertook a change detection memory task that assessed recollection of item-specific and spatial details. Participants studied rendered indoor and outdoor scenes and, in a subsequent recognition memory test, distinguished scenes that had not changed from those that had either undergone an item change (a different item exemplar) or a relational (spatial) change, which was followed by a subjective recollection judgment. The ASC group identified fewer item changes and spatial changes, to a similar degree, which was attributable to a specific reduction in recollection-based recognition relative to the control group. These findings provide evidence that recollection deficits in ASC may not be driven entirely by a relational binding deficit.This research was supported by a James S. McDonnell Scholar Award to J.S.S., an Economic and Social Research Council Award to R.A.C., and Leverhulme Trust Visiting Professorship and Parke Davis Exchange Fellowship Awards to C.R.This is the author accepted manuscript. The final version is available from he American Psychological Association via http://dx.doi.org/10.1037/abn000007

The role of tool geometry in process damped milling

The complex interaction between machining structural systems and the cutting process results in machining instability, so called chatter. In some milling scenarios, process damping is a useful phenomenon that can be exploited to mitigate chatter and hence improve productivity. In the present study, experiments are performed to evaluate the performance of process damped milling considering different tool geometries (edge radius, rake and relief angles and variable helix/pitch). The results clearly indicate that variable helix/pitch angles most significantly increase process damping performance. Additionally, increased cutting edge radius moderately improves process damping performance, while rake and relief angles have a smaller and closely coupled effect