Cell-type-specific optogenetic stimulation of the locus coeruleus induces slow-onset potentiation and enhances everyday memory in rats

Memory formation is typically divided into phases associated with encoding, storage, consolidation, and retrieval. The neural determinants of these phases are thought to differ. This study first investigated the impact of the experience of novelty in rats incurred at a different time, before or after, the precise moment of memory encoding. Memory retention was enhanced. Optogenetic activation of the locus coeruleus mimicked this enhancement induced by novelty, both when given before and after the moment of encoding. Optogenetic activation of the locus coeruleus also induced a slow-onset potentiation of field potentials in area CA1 of the hippocampus evoked by CA3 stimulation. Despite the locus coeruleus being considered a primarily noradrenergic area, both effects of such stimulation were blocked by the dopamine D1/D5 receptor antagonist SCH 23390. These findings substantiate and enrich the evidence implicating the locus coeruleus in cellular aspects of memory consolidation in hippocampus.</p

The Impact of Different Classification Criteria Sets on the Estimated Prevalence and Associated Risk Factors of Diastolic Dysfunction in Rheumatoid Arthritis

This study compared the estimated prevalence and potential determinants of left ventricular (LV) diastolic dysfunction upon applying different classification criteria in rheumatoid arthritis (RA). LV diastolic function was assessed echocardiographically by pulsed Doppler (E/A), tissue Doppler (E/e′, lateral and septal e′), and left atrial volume index in 176 RA patients. Relationships of traditional cardiovascular risk factors and RA characteristics with LV diastolic function and dysfunction according to previous and current criteria were determined in multivariate regression models. Waist-hip ratio was associated with E/A (standardised β (SE) = -0.28±0.09, p=0.0002) and lateral e′ (standardised β (SE) = 0.26±0.09, p=0.01); low diastolic blood pressure was related to E/e′ (standardised β (SE) = -0.16±0.08, p=0.04). Diastolic dysfunction prevalence differed upon applying previous (59%) compared to current (22%) criteria (p<0.0001). One SD increase in waist-hip ratio was associated with diastolic dysfunction when applying current criteria (OR = 2.61 (95% CI = 1.51–4.52), p=0.0006), whereas one SD increase in diastolic blood pressure was inversely related to diastolic dysfunction upon using previous criteria (OR = 0.57 (95% CI = 0.40–0.81), p=0.002). In conclusion, application of current and previous diastolic dysfunction criteria markedly alters the prevalence and risk factors associated with diastolic dysfunction in RA

Validation of methods for converting the original Disease Activity Score (DAS) to the DAS28

© The Author(s) 2018.The Disease Activity Score (DAS) is integral in tailoring the clinical management of rheumatoid arthritis (RA) patients and is an important measure in clinical research. Different versions have been developed over the years to improve reliability and ease of use. Combining the original DAS and the newer DAS28 data in both contemporary and historical studies is important for both primary and secondary data analyses. As such, a methodologically robust means of converting the old DAS to the new DAS28 measure would be invaluable. Using data from The Early RA Study (ERAS), a sub-sample of patients with both DAS and DAS28 data were used to develop new regression imputation formulas using the total DAS score (univariate), and using the separate components of the DAS score (multivariate). DAS were transformed to DAS28 using an existing formula quoted in the literature, and the newly developed formulas. Bland and Altman plots were used to compare the transformed DAS with the recorded DAS28 to ascertain levels of agreement. The current transformation formula tended to overestimate the true DAS28 score, particularly at the higher end of the scale. A formula which uses all separate components of the DAS was found to estimate the scores with a higher level of precision. A new formula is proposed that can be used by other early RA cohorts to convert the original DAS to DAS28.Peer reviewedFinal Published versio

Effects of Nitrogen and Planting Seed Size on Cotton Growth, Development, and Yield

A standardized experiment was conducted during 2009 and 2010 at 20 location-years across U.S. cotton (Gossypium hirsutum L.)-producing states to compare the N use requirement of contemporary cotton cultivars based on their planting seed size. Treatments consisted of three cotton varieties with planting seed of different numbers of seed per kg and N rates of 0, 45, 90, and 134 kg ha⁻¹. Soil at each trial location was sampled and tested for nitrate presence. High levels of soil nitrate (>91 N-NO₃⁻kg ha⁻¹) were found in Arizona and western Texas, and soil nitrate in the range of 45 to 73 kg N-NO₃⁻ ha⁻¹ was found at locations in the central United States. Cotton lint yield responded to applied N at 11 of 20 locations. Considering only sites that responded to applied N, highest lint yields were achieved with 112 to 224 kg ha⁻¹of applied plus pre-plant residual soil NO₃—translating to an optimal N requirement of 23 kg ha⁻¹ per 218 kg bale of lint produced. Among the varieties tested those with medium-sized seed produced higher yields in response to N than did larger and smaller seeded varieties. Varieties with larger seed had longer and stronger fibers, higher fiber length uniformity than small seeded varieties and decreased micronaire. Seed protein and oil increased and decreased slightly in response to increasing amounts of soil nitrate plus applied N, respectively

Adjuvant tyrosine kinase inhibitor therapy improves outcome for children and adolescents with acute lymphoblastic leukaemia who have an ABL‐class fusion

Patients with an ABL‐class fusion have a high risk of relapse on standard chemotherapy but are sensitive to tyrosine kinase inhibitors (TKI). In UKALL2011, we screened patients with post‐induction MRD ≥1% and positive patients (12%) received adjuvant TKI. As the intervention started during UKALL2011, not all eligible patients were screened prospectively. Retrospective screening of eligible patients allowed the outcome of equivalent ABL‐class patients who did and did not receive a TKI in first remission to be compared. ABL‐class patients who received a TKI in first remission had a reduced risk of relapse/refractory disease: 0% vs. 63% at four years (P = 0·009)

Communications Biophysics

Contains reports on four research projects.National Institutes of Health (Grant 5 P01 NS13126-02)National Institutes of Health (Grant 5 K04 NS00113-03)National Institutes of Health (Grant 2 ROI NS11153-02A1)National Science Foundation (Grant BNS77-16861)National Institutes of Health (Grant 5 RO1 NS10916-03)National Institutes of Health (Fellowship 1 F32 NS05327)National Institutes of Health (Grant 5 ROI NS12846-02)National Institutes of Health (Fellowship 1 F32 NS05266)Edith E. Sturgis FoundationNational Institutes of Health (Grant 1 R01 NS11680-01)National Institutes of Health (Grant 2 RO1 NS11080-04)National Institutes of Health (Grant 5 T32 GIM107301-03)National Institutes of Health (Grant 5 TOI GM01555-10