Does limited working memory capacity underlie age differences in associative long-term memory?

Past research has consistently shown that episodic memory (EM) declines with adult age and, according to the associative-deficit hypothesis, the locus of this decline is binding difficulties. We investigated the importance of establishing and maintaining bindings in working memory (WM) for age differences in associative EM. In Experiment 1 we adapted the presentation rate of word pairs for each participant to achieve 67% correct responses during a WM test of bindings in young and older adults. EM for the pairs was tested thereafter in the same way as WM. Equating WM for bindings between young and older adults reduced, but did not fully eliminate, the associative EM deficit in the older adults. In Experiment 2 we varied the set size of word pairs in a WM test, retaining the mean presentation rates for each age group from Experiment 1. If a WM deficit at encoding causes the EM deficit in older adults, both WM and EM performance should decrease with increasing set size. Against this prediction, increasing set size did not affect EM. We conclude that reduced WM capacity does not cause the EM deficit of older adults. Rather, both WM and EM deficits are reflections of a common cause, which can be compensated for by longer encoding time

Inspirationen und Impulse auf der WiTa

Die 16. Ausgabe der Wissenschaftstagung Ökologischer Landbau (WiTa) fand nach vier Jahren Corona-Pause von 8. bis 10. März unter dem Motto „One Step Ahead – einen Schritt voraus!“ auf dem neuen Campus des Forschungsinstituts für biologischen Landbau (FiBL) statt und regte spannende Diskussionen zu aktuellen, aberauch künftigen Fragen rund um die ökologische Land- und Lebensmittelwirtschaft an. Am 8. März begrüßte das FiBL über 300 Gäste zur WiTa, die als bedeutendste Plattform für den Austausch von Forschungsergebnissen der Ökolandwirtschaft im deutschsprachigen Raum gilt. Unter der Trägerschaft der Stiftung Ökologie & Landbau (SÖL) und des FiBL e.V. findet die Tagung in der Regel alle zwei Jahre an wechselnden Standorten statt. Die 16. Ausgabe wurde vom FiBL Schweiz gemeinsam mit der FiBL Projekte GmbH veranstaltet. In den rund dreieinhalb Tagen fanden sieben Exkursionen statt, außerdem konnten die Teilnehmenden 154 Vorträgen lauschen, 102 Poster-Präsentationen begutachten und 14 Workshops sowie sechs Science Pitches besuchen

The Effect of Non-specific Response Inhibition Training on Alcohol Consumption: An Intervention

Objective: Excessive alcohol consumption increases the risk of alcohol-related disease and injury. Poor response inhibition; the inability to intentionally override a pre-potent response, has been associated with greater alcohol consumption. The aim of the present study was to clarify if non-specific response inhibition training could improve response inhibition, and reduce alcohol consumption. Method: One hundred and sixty-eight undergraduates were randomly assigned to either an inhibition or active control condition, and completed a stop-signal task once a day for four consecutive days. The inhibition condition comprised a stop-signal task with a high target density (50% stop-signals), while the active control comprised a stop-signal task with a lower target density (25% stop-signals) and the instruction to ignore the signal. Before and after the intervention, participants completed measures of response inhibition, and alcohol consumption. Alcohol consumption was measured again at one month post-training. All parts of the study were completed online. Results: Contrary to the hypotheses, participants in the inhibition condition did not have lower levels of alcohol consumption, nor improved response inhibition after the intervention, compared to participants in the active control condition. Conclusion: It is suggested that response inhibition training needs to be specific to the target behaviour in order to be effective; however, that training did not improve response inhibition itself, calls into question the efficacy of this particular training paradigm. It is recommended that future response inhibition training paradigms consider how training intensity, and the format of administration, influences behavioural outcomes

Dissociating refreshing and elaboration and their impacts on memory

Maintenance of information in working memory (WM) is assumed to rely on refreshing and elaboration, but clear mechanistic descriptions of these cognitive processes are lacking, and it is unclear whether they are simply two labels for the same process. This fMRI study investigated the extent to which refreshing, elaboration, and repeating of items in WM are distinct neural processes with dissociable behavioral outcomes in WM and long-term memory (LTM). Multivariate pattern analyses of fMRI data revealed differentiable neural signatures for these processes, which we also replicated in an independent sample of older adults. In some cases, the degree of neural separation within an individual predicted their memory performance. Elaboration improved LTM, but not WM, and this benefit increased as its neural signature became more distinct from repetition. Refreshing had no impact on LTM, but did improve WM, although the neural discrimination of this process was not predictive of the degree of improvement. These results demonstrate that refreshing and elaboration are separate processes that differently contribute to memory performance

Does limited working memory capacity underlie age differences in associative long-term memory?

Past research has consistently shown that episodic memory (EM) declines with adult age and, according to the associative-deficit hypothesis, the locus of this decline is binding difficulties. We investigated the importance of establishing and maintaining bindings in working memory (WM) for age differences in associative EM. In Experiment 1 we adapted the presentation rate of word pairs for each participant to achieve 67% correct responses during a WM test of bindings in young and older adults. EM for the pairs was tested thereafter in the same way as WM. Equating WM for bindings between young and older adults reduced, but did not fully eliminate, the associative EM deficit in the older adults. In Experiment 2 we varied the set size of word pairs in a WM test, retaining the mean presentation rates for each age group from Experiment 1. If a WM deficit at encoding causes the EM deficit in older adults, both WM and EM performance should decrease with increasing set size. Against this prediction, increasing set size did not affect EM. We conclude that reduced WM capacity does not cause the EM deficit of older adults. Rather, both WM and EM deficits are reflections of a common cause, which can be compensated for by longer encoding time. (PsycINFO Database Record (c) 2018 APA, all rights reserved)

Clarifying the concept of chronic kidney disease for non-nephrologists

Chronic kidney disease (CKD) expands the prior concept of chronic renal insufficiency by including patients with relatively preserved renal function, as assessed by the estimated glomerular filtration rate (eGFR), as even these early CKD stages are associated with an increased risk for all-cause death and cardiovascular death, CKD progression and acute kidney injury. A decreased eGFR (3 months. However, when eGFR is 60 mL/min/1.73m2, an additional criterion is required to diagnose CKD. In a recent clinical trial published in The New England Journal of Medicine, all 6190 participants were reported to have CKD: 47% had Stages 1 and 2 CKD and 53% had Stage 3 CKD. This illustrates a widespread misunderstanding of the concept of CKD. Moreover, CKD categories in this study were assigned based on the estimated creatinine clearance. Since both estimated creatinine clearance and creatinine clearance overestimate eGFR, this illustrates another frequent misunderstanding: equating GFR with creatinine clearance. In this commentary, we clarify the concept of CKD and of CKD categories for non-nephrologists. Assigning a diagnosis of CKD to a patient with normal renal function and absence of other evidence of CKD may have negative consequences for the individual (e.g. insurance and others) as well as for the medical community at large by creating confusion about the concept.This research was supported by FIS PI16/02057, ISCIII-RETIC REDinREN RD016/0009 FEDER funds, Sociedad Española de Nefrología, Fundación Renal Iñigo Ávarez de Toledo (FRIAT), ISCIII Rio Hortega (MVPG) and Comunidad de Madrid Biomedicina B2017/BMD-3686 CIFRA2-CM

Resistance to mesenchymal reprogramming sustains clonal propagation in metastatic breast cancer

The acquisition of mesenchymal traits is considered a hallmark of breast cancer progression. However, the functional relevance of epithelial-to-mesenchymal transition (EMT) remains controversial and context dependent. Here, we isolate epithelial and mesenchymal populations from human breast cancer metastatic biopsies and assess their functional potential in vivo. Strikingly, progressively decreasing epithelial cell adhesion molecule (EPCAM) levels correlate with declining disease propagation. Mechanistically, we find that persistent EPCAM expression marks epithelial clones that resist EMT induction and propagate competitively. In contrast, loss of EPCAM defines clones arrested in a mesenchymal state, with concomitant suppression of tumorigenicity and metastatic potential. This dichotomy results from distinct clonal trajectories impacting global epigenetic programs that are determined by the interplay between human ZEB1 and its target GRHL2. Collectively, our results indicate that susceptibility to irreversible EMT restrains clonal propagation, whereas resistance to mesenchymal reprogramming sustains disease spread in multiple models of human metastatic breast cancer, including patient-derived cells in vivo

Extensive DNA End Processing by Exo1 and Sgs1 Inhibits Break-Induced Replication

Homology-dependent repair of DNA double-strand breaks (DSBs) by gene conversion involves short tracts of DNA synthesis and limited loss of heterozygosity (LOH). For DSBs that present only one end, repair occurs by invasion into a homologous sequence followed by replication to the end of the chromosome resulting in extensive LOH, a process called break-induced replication (BIR). We developed a BIR assay in Saccharomyces cerevisiae consisting of a plasmid with a telomere seeding sequence separated from sequence homologous to chromosome III by an I-SceI endonuclease recognition site. Following cleavage of the plasmid by I-SceI in vivo, de novo telomere synthesis occurs at one end of the vector, and the other end invades at the homologous sequence on chromosome III and initiates replication to the end of the chromosome to generate a stable chromosome fragment (CF). BIR was infrequent in wild-type cells due to degradation of the linearized vector. However, in the exo1Δ sgs1Δ mutant, which is defective in the 5′-3′ resection of DSBs, the frequency of BIR was increased by 39-fold. Extension of the invading end of the plasmid was detected by physical analysis two hours after induction of the I-SceI endonuclease in the wild-type exo1Δ, sgs1Δ, and exo1Δ sgs1Δ mutants, but fully repaired products were only visible in the exo1Δ sgs1Δ mutant. The inhibitory effect of resection was less in a plasmid-chromosome gene conversion assay, compared to BIR, and products were detected by physical assay in the wild-type strain. The rare chromosome rearrangements due to BIR template switching at repeated sequences were increased in the exo1Δ sgs1Δ mutant, suggesting that reduced resection can decrease the fidelity of homologous recombination

Outcomes of cerebral venous thrombosis due to vaccine-induced immune thrombotic thrombocytopenia after the acute phase

© 2022 American Heart Association, Inc.Background: Cerebral venous thrombosis (CVT) due to vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe condition, with high in-hospital mortality rates. Here, we report clinical outcomes of patients with CVT-VITT after SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) vaccination who survived initial hospitalization. Methods: We used data from an international registry of patients who developed CVT within 28 days of SARS-CoV-2 vaccination, collected until February 10, 2022. VITT diagnosis was classified based on the Pavord criteria. Outcomes were mortality, functional independence (modified Rankin Scale score 0–2), VITT relapse, new thrombosis, and bleeding events (all after discharge from initial hospitalization). Results: Of 107 CVT-VITT cases, 43 (40%) died during initial hospitalization. Of the remaining 64 patients, follow-up data were available for 60 (94%) patients (37 definite VITT, 9 probable VITT, and 14 possible VITT). Median age was 40 years and 45/60 (75%) patients were women. Median follow-up time was 150 days (interquartile range, 94–194). Two patients died during follow-up (3% [95% CI, 1%–11%). Functional independence was achieved by 53/60 (88% [95% CI, 78%–94%]) patients. No new venous or arterial thrombotic events were reported. One patient developed a major bleeding during follow-up (fatal intracerebral bleed). Conclusions: In contrast to the high mortality of CVT-VITT in the acute phase, mortality among patients who survived the initial hospitalization was low, new thrombotic events did not occur, and bleeding events were rare. Approximately 9 out of 10 CVT-VITT patients who survived the acute phase were functionally independent at follow-up.This study was funded by the Netherlands Organisation for Health Research and Development (ZonMw, grant number 10430072110005), the Dr. C.J. Vaillant Foundation, and Hospital District of Helsinki and Uusimaa (grant TYH2022223).info:eu-repo/semantics/publishedVersio

Male offspring born to mildly ZIKV-infected mice are at risk of developing neurocognitive disorders in adulthood

Congenital Zika virus (ZIKV) syndrome may cause fetal microcephaly in -1% of affected newborns. Here, we investigate whether the majority of clinically inapparent newborns might suffer from long-term health impairments not readily visible at birth. Infection of immunocompetent pregnant mice with high-dose ZIKV caused severe offspring phenotypes, such as fetal death, as expected. By contrast, low-dose (LD) maternal ZIKV infection resulted in reduced fetal birth weight but no other obvious phenotypes. Male offspring born to LD ZIKV-infected mothers had increased testosterone (TST) levels and were less likely to survive in utero infection compared to their female littermates. Males also presented an increased number of immature neurons in apical and basal hippocampal dendrites, while female offspring had immature neurons in basal dendrites only. Moreover, male offspring with high but not very high (storm) TST levels were more likely to suffer from learning and memory impairments compared to females. Future studies are required to understand the impact of TST on neuropathological and neurocognitive impairments in later life. In summary, increased sex-specific vigilance is required in countries with high ZIKV prevalence, where impaired neurodevelopment may be camouflaged by a healthy appearance at birth.Peer reviewe