Residue-specific structures and membrane locations of pH-low insertion peptide by solid-state nuclear magnetic resonance

The pH-low insertion peptide (pHLIP) binds to a membrane at pH 7.4 unstructured but folds across the bilayer as a transmembrane helix at pH similar to 6. Despite their promising applications as imaging probes and drug carriers that target cancer cells for cytoplasmic cargo delivery, the mechanism of pH modulation on pHLIP-membrane interactions has not been completely understood. Here, we show the first study on membrane-associated pHLIP using solid-state NMR spectroscopy. Data on residue-specific conformation and membrane location describe pHLIP in various surface-bound and membrane-inserted states at pH 7.4, 6.4 and 5.3. The critical membrane-adsorbed state is more complex than previously envisioned. At pH 6.4, for the major unstructured population, the peptide sinks deeper into the membrane in a state II\u27 that is distinct from the adsorbed state II observed at pH 7.4, which may enable pHLIP to sense slight change in acidity even before insertion

Bis(1H-benzimidazole-κN 3)bis­[2-(naphthalen-1-yl)acetato-κ2 O,O′]manganese(II) monohydrate

In the title compound, [Mn(C12H9O2)2(C7H6N2)2]·H2O, the MnII ion is located on a twofold rotation axis and six-coordinated, displaying a distorted MnN2O4 octa­hedral geometry. The crystal packing is stabilized by N—H⋯O hydrogen bonds, which give rise to a one-dimensional structure along [001], and π–π inter­actions between the imidazole rings and between the benzene rings of the 2-(naphthalen-1-yl)acetate ligands [centroid–centroid distances = 3.761 (3) and 3.728 (4) Å]. The contribution of the electron density associated with the disordered water molecules was not considerd in the final structure model

Efficacy of multidomain interventions to improve physical frailty, depression and cognition: data from cluster- randomized controlled trials

BackgroundFrailty is the pre- eminent exigency of aging. Although frailty- related impairments are preventable, and multidomain interventions appear more effective than unimodal ones, the optimal components remain uncertain.MethodsWe devised multidomain interventions against physical and cognitive decline among prefrail/frail community- dwelling - ¥65- year- olds and evaluated these in complementary cluster- randomized trials of efficacy and participant empowerment. The Efficacy Study compared ~3- monthly telephone consultations vs. 16, 2 h sessions/year comprising communally partaken physical and cognitive training plus nutrition and disease education; the Empowerment Study compared the standard Efficacy Study multidomain intervention (Sessions 1- 10) vs. an enhanced version redesigned to empower and motivate individual participants. Changes from baseline in physical, functional, and cognitive performance were measured after 6 and 12 months in the Efficacy Study and after 6 months in the Empowerment Study, with post- intervention follow- up at 9 months. Primary outcomes are as follows: Cardiovascular Health Study frailty score; gait speed; handgrip strength; and Montreal Cognitive Assessment (MoCA). Secondary outcomes are as follows: instrumental activities of daily living; metabolic equivalent of task (MET); depressed mood (Geriatric Depression Scale- 5 - ¥2); and malnutrition (Mini- Nutritional Assessment short- form - ¤11). Intervention effects were analyzed using a generalized linear mixed model.ResultsEfficacy Study participants (n = 1082, 40 clusters) were 75.1 ± 6.3 years old, 68.7% women, and 64.7% prefrail/frail; analytic clusters: 19 intervention (410/549 completed) vs. 21 control (375/533 completed). Empowerment Study participants (n = 440, 14 clusters) were 75.9 ± 7.1 years old, 83.6% women, and 56.7% prefrail/frail; analytic clusters: seven intervention (209/230 completed) vs. seven control (189/210 completed). The standard and enhanced multidomain interventions both reduced frailty and significantly improved aspects of physical, functional, and cognitive performance, especially among - ¥75- year- olds. Standard multidomain intervention decreased depression [odds ratio 0.56, 95% confidence interval (CI) 0.32, 0.99] and malnutrition (odds ratio 0.45, 95% CI 0.26, 0.78) by 12 months and improved concentration at Months 6 (0.23, 95% CI 0.04, 0.42) and 12 (0.46, 95% CI 0.22, 0.70). Participant empowerment augmented activity (4.67 MET/h, 95% CI 1.64, 7.69) and gait speed (0.06 m/s, 95% CI 0.00, 0.11) at 6 months, with sustained improvements in delayed recall (0.63, 95% CI 0.20, 1.06) and MoCA performance (1.29, 95% CI 0.54, 2.03), and less prevalent malnutrition (odds ratio 0.39, 95% CI 0.18, 0.84), 3 months after the intervention ceased.ConclusionsPragmatic multidomain intervention can diminish physical frailty, malnutrition, and depression and enhance cognitive performance among community- dwelling elders, especially - ¥75- year- olds; this might supplement healthy aging policies, probably more effectively if participants are empowered.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/156002/1/jcsm12534.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/156002/2/10.1002_jcsm.12534_Fig_S4.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/156002/3/jcsm12534_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/156002/4/10.1002_jcsm.12534_Fig_S2.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/156002/5/10.1002_jcsm.12534_Table_S3.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/156002/6/10.1002_jcsm.12534_Fig_S3.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/156002/7/10.1002_jcsm.12534_Appendix_S1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/156002/8/10.1002_jcsm.12534_Table_S2.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/156002/9/10.1002_jcsm.12534_Table_S1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/156002/10/10.1002_jcsm.12534_Fig_S1.pd

Clinical Study Heart Rate Variability Analysis in Patients with Allergic Rhinitis

Background. Very few studies investigate the role of the autonomic nervous system in allergic rhinitis. In this study, we evaluated the autonomic nervous system in allergic rhinitis patients using heart rate variability (HRV) analysis. Methods. Eleven patients with allergic rhinitis and 13 healthy controls, aged between 19 and 40 years old, were enrolled in the study. Diagnosis of allergic rhinitis was based on clinical history, symptoms, and positive Phadiatop test. Electrocardiographic recordings on the sitting and supine positions were obtained for HRV analysis. Results. In the supine position, there were no significant statistical differences in verylow-frequency power (VLF, ≤0.04 Hz), low-frequency power (LF, 0.04-0.15 Hz), high-frequency power (HF, 0.15-0.40 Hz), and the ratio of LF to HF (LF/HF) between the patient and control groups. The mean RR intervals significantly increased, while LF% and LF/HF significantly decreased in the patient group in the sitting position. Moreover, mean RR intervals, LF, and LF/HF, which were significantly different between the two positions in the control group, did not show a significant change with the posture change in the patient group. Conclusion. These suggest that patients with allergic rhinitis may have poor sympathetic modulation in the sitting position. Autonomic dysfunction may therefore play a role in the pathophysiology of allergic rhinitis

Effect of Nitrogen Content on Hot Deformation Behavior and Grain Growth in Nuclear Grade 316LN Stainless Steel

316LN stainless steel with 0.08%N (08N) and 0.17%N (17N) was compressed at 1073–1473 K and 0.001–10 s−1. The hot deformation behavior was investigated using stress-strain curve analysis, processing maps, and so forth. The microstructure was analyzed through electron backscatter diffraction analysis. Under most conditions, the deformation resistance of 17N was higher than that of 08N. This difference became more pronounced at lower temperatures. The strain rate sensitivity increased with increasing temperature for types of steel. In addition, the higher the N content, the higher the strain rate sensitivity. Hot deformation activation energy increased from 487 kJ/mol to 549 kJ/mol as N concentration was increased from 0.08% to 0.17%. The critical strain for initiation of dynamic recrystallization was lowered with increasing N content. In the processing maps, both power dissipation ratio and unstable region increased with increasing N concentration. In terms of microstructure evolution, N promoted dynamic recrystallization kinetic and decreased dynamic recrystallization grain size. The grain growth rate was lower in 17N than in 08N during heat treatment. Finally, it was found that N favored twin boundary formation

Heart Rate Variability Analysis in Patients with Allergic Rhinitis

Background. Very few studies investigate the role of the autonomic nervous system in allergic rhinitis. In this study, we evaluated the autonomic nervous system in allergic rhinitis patients using heart rate variability (HRV) analysis. Methods. Eleven patients with allergic rhinitis and 13 healthy controls, aged between 19 and 40 years old, were enrolled in the study. Diagnosis of allergic rhinitis was based on clinical history, symptoms, and positive Phadiatop test. Electrocardiographic recordings on the sitting and supine positions were obtained for HRV analysis. Results. In the supine position, there were no significant statistical differences in very-low-frequency power (VLF, ≤0.04 Hz), low-frequency power (LF, 0.04–0.15 Hz), high-frequency power (HF, 0.15–0.40 Hz), and the ratio of LF to HF (LF/HF) between the patient and control groups. The mean RR intervals significantly increased, while LF% and LF/HF significantly decreased in the patient group in the sitting position. Moreover, mean RR intervals, LF, and LF/HF, which were significantly different between the two positions in the control group, did not show a significant change with the posture change in the patient group. Conclusion. These suggest that patients with allergic rhinitis may have poor sympathetic modulation in the sitting position. Autonomic dysfunction may therefore play a role in the pathophysiology of allergic rhinitis

Development of a fluorescent quantitative real-time polymerase chain reaction assay for the detection of Goose parvovirus in vivo

<p>Abstract</p> <p>Background</p> <p>Goose parvovirus (GPV) is a <it>Dependovirus </it>associated with latent infection and mortality in geese. Currently, it severely affects geese production worldwide. The objective of this study was to develop a fluorescent quantitative real-time polymerase chain reaction (PCR) (FQ-PCR) assay for fast and accurate quantification of GPV DNA in infected goslings, which can aid in the understanding of the regular distribution pattern and the nosogenesis of GPV in vivo.</p> <p>Results</p> <p>The detection limit of the assay was 2.8 × 10¹standard DNA copies, with a sensitivity of 3 logs higher than that of the conventional gel-based PCR assay targeting the same gene. The real-time PCR was reproducible, as shown by satisfactory low intraassay and interassay coefficients of variation.</p> <p>Conclusion</p> <p>The high sensitivity, specificity, simplicity, and reproducibility of the GPV fluorogenic PCR assay, combined with a high throughput, make this method suitable for a broad spectrum of GPV etiology-related applications.</p