Classification of general and personal semantic details in the Autobiographical Interview

The Autobiographical Interview (AI) separates internal (episodic) and external (non-episodic) details from transcribed protocols using an exhaustive and reliable scoring system. While the details comprising the internal composite are centered on elements of episodic memory, external details are more heterogeneous as they are meant to capture a variety of non-episodic utterances: general semantics, different types of personal semantics details, metacognitive statements, repetitions, and details about off topic events. Elevated external details are consistently observed in aging and in neurodegenerative diseases. In the present study, we augmented the AI scoring system to differentiate subtypes of external details to test whether the elevation of these details in aging and in frontotemporal lobar degeneration (including mixed frontotemporal/semantic dementia [FTD/SD] and progressive non-fluent aphasia [PNFA]) would be specific to general and personal semantics or would concern all subtypes. Specifically, we separated general semantic details from personal semantic details (including autobiographical facts, self-knowledge, and repeated events). With aging, external detail elevation was observed for general and personal semantic details but not for other types of external details. In frontotemporal lobar degeneration, patients with FTD/SD (but not PNFA) generated an excess of personal semantic details but not general semantic details. The increase in personal but not general semantic details in FTD/SD is consistent with prevalent impairment of general semantic memory in SD, and with the personalization of concepts in this condition. Under standard AI instructions, external details were intended to capture off-topic utterances and were not intended as a direct measure of semantic abilities. Future investigations concerned with semantic processing in aging and in dementia could modify standard instructions of the AI to directly probe semantic content

Transition of plasmodium sporozoites into liver stage-like forms is regulated by the RNA binding protein pumilio

Many eukaryotic developmental and cell fate decisions that are effected post-transcriptionally involve RNA binding proteins as regulators of translation of key mRNAs. In malaria parasites (Plasmodium spp.), the development of round, non-motile and replicating exo-erythrocytic liver stage forms from slender, motile and cell-cycle arrested sporozoites is believed to depend on environmental changes experienced during the transmission of the parasite from the mosquito vector to the vertebrate host. Here we identify a Plasmodium member of the RNA binding protein family PUF as a key regulator of this transformation. In the absence of Pumilio-2 (Puf2) sporozoites initiate EEF development inside mosquito salivary glands independently of the normal transmission-associated environmental cues. Puf2- sporozoites exhibit genome-wide transcriptional changes that result in loss of gliding motility, cell traversal ability and reduction in infectivity, and, moreover, trigger metamorphosis typical of early Plasmodium intra-hepatic development. These data demonstrate that Puf2 is a key player in regulating sporozoite developmental control, and imply that transformation of salivary gland-resident sporozoites into liver stage-like parasites is regulated by a post-transcriptional mechanism

European Heart Rhythm Association (EHRA)/Heart Rhythm Society (HRS)/Asia Pacific Heart Rhythm Society (APHRS)/Latin American Heart Rhythm Society (LAHRS) expert consensus on risk assessment in cardiac arrhythmias: use the right tool for the right outcome, in the right population.

In clinical practice and for scientific purposes, cardiologists and primary care physicians perform risk assessment in patients with cardiac diseases or conditions with high risk of developing such. The European Heart Rhythm Association (EHRA), Heart Rhythm Society (HRS), Asia Pacific Heart Rhythm Society (APHRS), and the Latin American Heart Rhythm Society (LAHRS) set down this expert consensus statement task force to summarize the consensus regarding risk assessment in cardiac arrhythmias. Objectives were to raise awareness of using the right risk assessment tool for a given outcome in a given population, and to provide physicians with practical proposals that may lead to rational and evidence-based risk assessment and improvement of patient care in this regard. A large variety of methods are used for risk assessment and choosing the best methods and tools hereof in a given situation is not simple. Even though parameters and test results found associated with increased risk of one outcome (e.g. death) may also be associated with higher risk of other adverse outcomes, specific risk assessment strategies should be used only for the purposes for which they are validated. The work of this task force is summarized in a row of consensus statement tables

Older adults with lower autobiographical memory abilities report less age-related decline in everyday cognitive function

Abstract Background Individuals differ in how they remember the past: some richly re-experience specific details of past episodes, whereas others recall only the gist of past events. Little research has examined how such trait mnemonics, or lifelong individual differences in memory capacities, relate to cognitive aging. We specifically examined trait episodic autobiographical memory (AM, the tendency to richly re-experience episodic details of past events) in relation to complaints of everyday cognitive functioning, which are known to increase with age. Although one might predict that individuals reporting higher trait-level episodic AM would be resistant to age-related decline in everyday function, we made the opposite prediction. That is, we predicted that those with lower trait-level episodic AM would be better equipped with compensatory strategies, practiced throughout the lifespan, to cope with age-related memory decline. Those with higher trait-level episodic AM would have enhanced sensitivity to age-related cognitive changes due to their tendency to rely on their perceived above-average memory function. Methods We tested these predictions in 959 older adults aged 50–93 using online subjective and objective measures of memory and cognitive function. Our key measures of interest were the Survey of Autobiographical Memory, a measure of autobiographical memory abilities; and the Cognitive Failures Questionnaire, a measure of everyday cognitive function. Results In keeping with our prediction, we found that complaints of day-to-day memory slips and errors (normally elevated with age) remained stable or even decreased with age among those reporting lower trait-level episodic AM, whereas those reporting higher trait-level episodic AM reported the expected age-related increase in such errors. This finding was specific to episodic AM and not observed for other autobiographical memory capacities (e.g., semantic, spatial). It was further unaccounted for by response bias or objectively assessed cognitive abilities. Conclusions Congenitally low trait-level episodic AM may paradoxically confer a functional advantage in aging. This could be due to well-developed non-episodic strategies not present in those with higher abilities, who are more sensitive to age-related memory decline attributable to medial temporal lobe changes. Our findings emphasize the importance of considering individual differences when studying cognitive aging trajectories

Axl receptor tyrosine kinase is a regulator of apolipoprotein E

Alzheimer’s disease (AD), the leading cause of dementia, is a chronic neurodegenerative disease. Apolipoprotein E (apoE), which carries lipids in the brain in the form of lipoproteins, plays an undisputed role in AD pathophysiology. A high-throughput phenotypic screen was conducted using a CCF-STTG1 human astrocytoma cell line to identify small molecules that could upregulate apoE secretion. AZ7235, a previously discovered Axl kinase inhibitor, was identified to have robust apoE activity in brain microglia, astrocytes and pericytes. AZ7235 also increased expression of ATP-binding cassette protein A1 (ABCA1), which is involved in the lipidation and secretion of apoE. Moreover, AZ7235 did not exhibit Liver-X-Receptor (LXR) activity and stimulated apoE and ABCA1 expression in the absence of LXR. Target validation studies using AXL−/− CCF-STTG1 cells showed that Axl is required to mediate AZ7235 upregulation of apoE and ABCA1. Intriguingly, apoE expression and secretion was significantly attenuated in AXL-deficient CCF-STTG1 cells and reconstitution of Axl or kinase-dead Axl significantly restored apoE baseline levels, demonstrating that Axl also plays a role in maintaining apoE homeostasis in astrocytes independent of its kinase activity. Lastly, these effects may require human apoE regulatory sequences, as AZ7235 exhibited little stimulatory activity toward apoE and ABCA1 in primary murine glia derived from neonatal human APOE3 targeted-replacement mice. Collectively, we identified a small molecule that exhibits robust apoE and ABCA1 activity independent of the LXR pathway in human cells and elucidated a novel relationship between Axl and apoE homeostasis in human astrocytes.Medicine, Faculty ofOther UBCNon UBCPathology and Laboratory Medicine, Department ofReviewedFacult

Photosynthesis in relation to D1, PsaA and Rubisco in marine and brackish water ecotypes of Fucus vesiculosus and Fucus radicans (Phaeophyceae)

The aim of this study was to investigate photosynthetic differences between the marine, Norwegian Sea ecotype and the brackish, Bothnian Sea ecotype of F. vesiculosus and F. radicans and to see whether photosynthetic differences could be connected with the relative amounts of D1 protein (PSII), PsaA (PSI) protein and/or Rubisco. For this purpose, we tested if a higher photosynthetic maximum (P (max)) in the Atlantic Ocean ecotype of F. vesiculosus relative to the Baltic Sea ecotype, and an increase of the P (max) in Baltic Sea ecotype of F. vesiculosus at higher salinity, could be due to an increase in the relative amounts of Rubisco. The proteins have been evaluated on a relative basis. Immunoblot signals showed that the amount of Rubisco was higher in both ecotypes of F. vesiculosus than in F. radicans, but no differences could be detected between the two ecotypes of F. vesiculosus. The results suggest an uneven photosystem protein stoichiometry in Fucus, with more of the PSI protein PsaA relative to the PSII protein D1. The difference in P (max) between the two ecotypes of F. vesiculosus might be related to the difficulties for the algae to adapt to the environment in Bothnian Sea