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Dementia affects multiple aspects of cognitive functioning, including working memory and executive functioning. Memory self-efficacy (MSE) has previously been related to episodic memory performance and to executive functioning, but little research has examined the relations between MSE and working memory. United States older adults (N = 197) were recruited via MTurk to complete an MSE questionnaire before completing a digit span working memory task. Hierarchical regression results revealed that the model accounted for a significant amount of variance in working memory performance after statistically controlling for several covariates, F(11, 179) = 4.94, p <.001, adjusted R2 =.19. MSE explained a large and unique portion of variance (B = 1.02, SE = 0.17, p <.001). Based on our findings, one's beliefs about their memory are positively associated with their working memory performance. These novel findings provide support for neuropsychologists to consider using MSE measures and utilizing MSE interventions. [ABSTRACT FROM AUTHOR]

Advances in multi‐collector inductively coupled plasma‐mass spectrometry (MC‐ICP‐MS) have led to the widespread use of iron (Fe) isotopes to elucidate the (bio)geochemical history of a range of environments. To generate Fe isotope ratio measurements, standard‐sample bracketing (SSB) is commonly used to correct for instrumental mass bias inherent to MC‐ICP‐MS. However, SSB is only accurate when sample and isotope standard Fe concentrations match, in addition to the bulk solution matrix. When the Fe concentrations differ, Fe isotope ratio measurement results may be inaccurate, a phenomenon known as the "self‐induced matrix effect." This study systematically characterised the self‐induced matrix effect for dry plasma Fe isotope ratio measurements on three MC‐ICP‐MS instruments and three introduction systems. Our extensive dataset indicates that: (1) the degree of mass bias is consistent regardless of MC‐ICP‐MS front‐end design, (2) the degree of mass bias becomes less reproducible as the concentration difference between the sample and bracketing standard increases, and (3) this applies to both pure Fe solutions and solutions from geological materials. This study reinforces the requirement to match bracketing standard and sample concentrations within 10% and provides a correction method for that fall beyond the recommended concentration range to subsequently allow for proper concentration matching during SSB. [ABSTRACT FROM AUTHOR]

At the onset of the COVID-19 pandemic, providers of independent living services for rural disabled people were forced to adapt how they conducted their operations. This study is a primary analysis of data based on transcripts from eight meetings of a nationwide network of service providers (n = 40-150 participants per meeting), who met virtually to provide peer support during the unfolding pandemic. We used qualitative thematic analysis to understand the ways these service providers adapted to address the needs of rural disabled people during the pandemic. We identified four main themes describing organizational adaptations. Although this was a predominantly challenging time, service providers identified ways their adaptations were beneficial. These included creating new ways to connect, reaching more people with disabilities, and reducing commuting time to provide services. Service providers intended to continue using their adapted strategies and platforms for providing services, and thus projected these benefits would be long-lasting. [ABSTRACT FROM AUTHOR]

ObjectiveOlder individuals face a higher likelihood of developing dementia. The rate of cognitive decline resulting from dementia is not equivalent for all, as some patients with dementia are able to function independently longer than others, despite having similar disease burden. The cognitive reserve (CR) theory provides one explanation for the differing rate of decline. CR suggests that there are factors—most notably, educational attainment and occupational attainment—that can protect against the cognitive decline. Although the beneficial effects of these notable CR factors are clear, not all are easily modifiable. Participation in leisure activities may represent a more easily modifiable factor. Some research hints at beneficial effects of leisure activities, although specific leisure activities have not been well examined. The present study examined the relations between handicraft art leisure activities (HALAs) and multiple cognitive domains. MethodArchival WAIS-IV and demographic data for 50 California retirement community residents were examined. ResultsHALA participation accounted for statistically significant variance in working memory performance (R2 =.40, β =.24%) over and above the established CR factors of age, depression, educational attainment, and occupational attainment. In addition, HALA participation was related to a better ability to perform abstract visual information tasks (Block Design subtest, r =.28, p =.05) and non-verbal reasoning tasks (Visual Puzzles subtest, r =.38, p =.008). ConclusionsHALA participation among older adults could contribute to the retention of cognitive function, supporting the role of HALA participation as a CR factor. [ABSTRACT FROM AUTHOR]

Fission reactions result in Nd isotope decay products which alter Nd isotopic compositions measured in nuclear debris. Trinitite samples measured by MC-ICP-MS show perturbations of Nd isotopes relative to 142Nd, the only isotope of Nd which is blocked from fission product decay. By measuring 144Nd/142Nd and the total number of atoms of 142Nd in the sample, it is possible to quantify the total number of fissions in nuclear debris, an important signature in post-detonation nuclear forensics. [ABSTRACT FROM AUTHOR]

Background: Disease-modifying therapy (DMT) delays disease progression and improves quality of life for patients with multiple sclerosis (MS), but adherence to DMT is often suboptimal. Vanderbilt Specialty Pharmacy (VSP) embeds pharmacists within an outpatient MS clinic to provide medication management and address barriers to adherence. Objective: We evaluated rates and predictors of adherence to DMT among patients with MS at an integrated specialty pharmacy. Methods: We included patients with MS who filled ≥3 DMT prescriptions from VSP during the study period. Adherence was defined as medication possession ratio (MPR) or proportion of days covered (PDC) ≥0.8. Reasons for nonadherence were collected from pharmacy claims and electronic medical records. Results: The study included 653 patients. Average MPR and PDC were 0.93 and 0.94, respectively. Eighty-eight percent of patients achieved MPR ≥0.8; 89% achieved PDC ≥0.8. Using financial assistance and having $0 out-of-pocket cost were associated with higher odds of achieving MPR and PDC ≥0.8 (P <.05). Of the 12% of patients who were nonadherent, most were unreachable for refills. Conclusions: Ensuring financial assistance and low out-of-pocket costs are associated with high adherence to DMT within an integrated specialty clinic, but more work is needed to address adherence in unreachable patients. [ABSTRACT FROM AUTHOR]

PRDM9 is a PR domain containing protein which trimethylates histone 3 on lysine 4 and 36. Its normal expression is restricted to germ cells and attenuation of its activity results in altered meiotic gene transcription, impairment of double-stranded breaks and pairing between homologous chromosomes. There is growing evidence for a role of aberrant expression of PRDM9 in oncogenesis and genome instability. Here we report the discovery of MRK-740, a potent (IC50: 80 ± 16 nM), selective and cell-active PRDM9 inhibitor (Chemical Probe). MRK-740 binds in the substrate-binding pocket, with unusually extensive interactions with the cofactor S-adenosylmethionine (SAM), conferring SAM-dependent substrate-competitive inhibition. In cells, MRK-740 specifically and directly inhibits H3K4 methylation at endogenous PRDM9 target loci, whereas the closely related inactive control compound, MRK-740-NC, does not. The discovery of MRK-740 as a chemical probe for the PRDM subfamily of methyltransferases highlights the potential for exploiting SAM in targeting SAM-dependent methyltransferases. PRDM9 is a PR domain containing histone methyl transferase which expression is normally restricted to the germline that has also been linked to a number of somatic cancers. Here the authors describe the identification of a small molecule that selectivity inhibits the methyltransferase activity of PRDM9 in biochemical and cellular assays [ABSTRACT FROM AUTHOR]

Cultural norms for the experience, expression, and regulation of emotion vary widely between individualistic and collectivistic cultures. Collectivistic cultures value conformity, social harmony, and social status hierarchies, which demand sensitivity and focus to broader social contexts, such that attention is directed to contextual emotion information to effectively function within constrained social roles and suppress incongruent personal emotions. By contrast, individualistic cultures valuing autonomy and personal aspirations are more likely to attend to central emotion information and to reappraise emotions to avoid negative emotional experience. Here we examined how culture affects perceptual strategies employed during emotion regulation, particularly during cognitive reappraisal and emotional suppression. Eye movements were measured while healthy young adult participants viewed negative International Affective Picture System (IAPS) images and regulated emotions by using either strategies of reappraisal (19 Asian American, 21 Caucasian American) or suppression (21 Asian American, 23 Caucasian American). After image viewing, participants rated how negative they felt as a measure of subjective emotional experience. Consistent with prior studies, reappraisers made lower negative valence ratings after regulating emotions than suppressers across both Asian American and Caucasian American groups. Although no cultural variation was observed in subjective emotional experience during emotion regulation, we found evidence of cultural variation in perceptual strategies used during emotion regulation. During middle and late time periods of emotional suppression, Asian American participants made significantly fewer fixations to emotionally salient areas than Caucasian American participants. These results indicate cultural variation in perceptual differences underlying emotional suppression, but not cognitive reappraisal. [ABSTRACT FROM AUTHOR]

The present study used a synchronization-continuation paradigm during continuous bimanual drumming with different cues in 17 persons with Down syndrome, eight typical persons with similar mental age and eight typical persons with similar chronological age. The task required participants to hit two drums with their hands at the same time following music (e.g., a tune with various decibel drum beats), auditory (e.g., sound of drumbeat), verbal (e.g., voice saying "drum"), and visual (e.g., video of both hands moving up and down and hitting the drums together) cues for 10 seconds, then continue drumming in the absence of cues for another 10 seconds. In general, when all groups were following the music cues their movements were faster as compared with their movements in the auditory, verbal, and visual conditions. In addition, when following visual cues all groups produced more accurate and consistently coordinated movements than with the other cue types. Further, participants with Down syndrome often stopped moving when the pacing cues were eliminated indicating a need for continuous cues for continuous movements. [ABSTRACT FROM AUTHOR]

Parasitic nematodes negatively impact human and animal health worldwide. The market withdrawal of nematicidal agents due to unfavourable toxicities has limited the available treatment options. In principle, co-administering nematicides at lower doses along with molecules that potentiate their activity could mitigate adverse toxicities without compromising efficacy. Here, we screened for new small molecules that interact with aldicarb, which is a highly effective treatment for plant-parasitic nematodes whose toxicity hampers its utility. From our collection of 638 worm-bioactive compounds, we identified 20 molecules that interact positively with aldicarb to either kill or arrest the growth of the model nematode Caenorhabditis elegans. We investigated the mechanism of interaction between aldicarb and one of these novel nematicides called wact-86. We found that the carboxylesterase enzyme GES-1 hydrolyzes wact-86, and that the interaction is manifested by aldicarb’s inhibition of wact-86’s metabolism by GES-1. This work demonstrates the utility of C. elegans as a platform to search for new molecules that can positively interact with industrial nematicides, and provides proof-of-concept for prospective discovery efforts. [ABSTRACT FROM AUTHOR]

The present study used a synchronization-continuation paradigm during continuous bimanual drumming with different cues in 17 persons with Down syndrome, eight typical persons with similar mental age and eight typical persons with similar chronological age. The task required participants to hit two drums with their hands at the same time following music (e.g., a tune with various decibel drum beats), auditory (e.g., sound of drumbeat), verbal (e.g., voice saying "drum"), and visual (e.g., video of both hands moving up and down and hitting the drums together) cues for 10 seconds, then continue drumming in the absence of cues for another 10 seconds. In general, when all groups were following the music cues their movements were faster as compared with their movements in the auditory, verbal, and visual conditions. In addition, when following visual cues all groups produced more accurate and consistently coordinated movements than with the other cue types. Further, participants with Down syndrome often stopped moving when the pacing cues were eliminated indicating a need for continuous cues for continuous movements. [ABSTRACT FROM AUTHOR]

Insulin resistance is a prominent feature in heart failure, while hyperglycemia impairs cardiac contraction. We propose that decreased insulin-mediated glucose uptake by the heart preserves cardiac function in response to metabolic and hemodynamic stress. To test this hypothesis, we fed rats a high-sucrose diet (HSD). Energy substrate metabolism and cardiac work were determined ex vivo in a sequential protocol simulating metabolic and hemodynamic stress. Compared to chow-fed, control rats, HSD impaired myocardial insulin responsiveness and induced profound metabolic changes in the heart, characterized by reduced rates of glucose uptake (7.91 ±0.30 vs. 10.73±0.67 µmol/min/g dry weight; P<0.001) but increased rates of glucose oxidation (2.38±0.17 vs. 1.50±0.15 (i.mol/min/g dry weight; P<0.001) and oleate oxidation (2.29±0.11 vs. 1.96±0.12 µmol/min/g dry weight; P<0.05). Tight coupling of glucose uptake and oxidation and improved cardiac efficiency were associated with a reduction in glucose 6-phosphate and oleoyl-CoA levels, as well as a reduction in the content of uncoupling protein 3. Our results suggest that insulin resistance lessens fuel toxicity in the stressed heart. This calls for a new exploration of the mechanisms regulating substrate uptake and oxidation in the insulin-resistant heart. [ABSTRACT FROM AUTHOR]

Perception of affordances research in children with developmental disabilities has only examined well practiced skills. Ten toddlers with Down syndrome and 10 with typical development walked across a GAITRite mat, with and without an obstacle. We coded the toddlers' behaviors after 1 and 3 months of walking experience when they encountered the obstacle (avoid, crawl, error, and walk successfully) and calculated gait parameters (step length, width, and velocity). Both groups actively explored their affordances. Despite similar decreases in step length and velocity when approaching the obstacle, toddlers with Down syndrome were more likely to select successful but conservative crawling strategies that minimized balance requirements and reduced risk of falling. Group differences were due to risk management rather than difficulty perceiving affordances. [ABSTRACT FROM AUTHOR]

Symmetry groups-rules that connect different configurations of a given set of components-represent a compact means of coding for effects, a feature that is desirable in both model- and theory-building. The present study was designed to compare the effects of spatial orientation differences with the various other asymmetries (e.g., timing differences, handedness preferences, the direction of attention) that are accommodated by current models of bimanual coordination. The authors used symmetry groups to predict specific patterns of results. In 2 experiments, participants (N 13, Experiment 1; N= 9, Experiment 2) coordinated the movements of differently oriented (1 downward and 1 upward) pendulum pairs at a low (0.62 Hz) or high (0.82 Hz) movement frequency to establish an in-phase or antiphase pattern. Consistent with previous results (P. G. Amazeen, E. L. Amazeen, & M. T. Turvey, 1998a), the downward-oriented pendulum tended to lead slightly. In contrast to the effects of other bimanual asymmetries, the downward-oriented pendulum lead was amplified at low frequencies. Although the results contradicted the predictions of existing models of bimanual coordination, they were consistent with predictions from symmetry group theory. In the discussion, the authors focus on the application of symmetry groups to both bimanual coordination and other phenomena with more complex symmetric structures. [ABSTRACT FROM AUTHOR]

An experiment was designed to evaluate later timing of fixed-time artificial insemination (FTAI) with sexsorted semen among postpartum beef cows following the 7 & 7 Synch protocol, with the hypothesis that later timing would result in increased pregnancy rates (P/AI) among cows that expressed estrus prior to FTAI. Beef cows (n = 414) were blocked based on age and days postpartum (DPP) and randomly assigned to receive FTAI at 66 or 72 h after administration of prostaglandin F2a (PG). Estrus was synchronized using the 7 & 7 Synch protocol, which consists of administration of PG (500 µg cloprostenol) and insertion of an intravaginal progesterone-releasing insert (CIDR; 1.38 g progesterone) on Day 0, gonadotropin-releasing hormone (GnRH; 100 µg gonadorelin) on Day 7, and PG coincident with CIDR removal on Day 14. Estrus detection aids (EstrotectTM) were applied to all cows on Day 14, and activation status was recorded at fixedtime artificial insemination (FTAI) on Day 17. All cows that expressed estrus prior to FTAI received sex-sorted semen (4 × 106 cells per unit; SexedULTRA 4MTM). The proportion of cows expressing estrus prior to FTAI did not differ between treatments at this power of test [66 h: 71% (146/205); 72 h: 76% (158/209)]. Additionally, P/AI of estrous cows inseminated with sex-sorted semen did not differ between treatments [66 h: 44% (90/205); 72 h: 39% (82/209)]. In conclusion, later timing of FTAI following the 7 & 7 Synch protocol failed to improve P/AI of estrous cows inseminated with sex-sorted semen. [ABSTRACT FROM AUTHOR]

The DAF-9 cytochrome P450 is a key regulator of dauer formation, developmental timing and longevity in the nematode Caenorhabditis elegans. Here we describe the first identified chemical inhibitor of DAF-9 and the first reported small-molecule tool that robustly induces dauer formation in typical culture conditions. This molecule (called dafadine) also inhibits the mammalian ortholog of DAF-9(CYP27A1), suggesting that dafadine can be used to interrogate developmental control and longevity in other animals. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

In embryonic stem cells, promoters of key lineage-specific differentiation genes are found in a bivalent state, having both activating H3K4me3 and repressive H3K27me3 histone marks, making them poised for transcription upon loss of H3K27me3. Whether cancer-initiating cells (C-ICs) have similar epigenetic mechanisms that prevent lineage commitment is unknown. Here we show that colorectal C-ICs (CC-ICs) are maintained in a stem-like state through a bivalent epigenetic mechanism. Disruption of the bivalent state through inhibition of the H3K27 methyltransferase EZH2, resulted in decreased self-renewal of patient-derived C-ICs. Epigenomic analyses revealed that the promoter of Indian Hedgehog (IHH), a canonical driver of normal colonocyte differentiation, exists in a bivalent chromatin state. Inhibition of EZH2 resulted in de-repression of IHH, decreased self-renewal, and increased sensitivity to chemotherapy in vivo. Our results reveal an epigenetic block to differentiation in CC-ICs and demonstrate the potential for epigenetic differentiation therapy of a solid tumour through EZH2 inhibition. The presence of bivalent epigenetic active and repressive histone marks control lineage-specific differentiation in embryonic stem cells. Here, the authors reveal that bivalent marks repress the differentiation gene IHH in colorectal cancer-initiating cells, and can be targeted by EZH2 inhibition [ABSTRACT FROM AUTHOR]

A correction to the article "Dafadine inhibits DAF-9 to promote dauer formation and longevity of Caenorhabditis elegans" that was published in the 2011 issue is presented.