The amyloid fibrils of beta-amyloid (Aβ) peptides play important roles in the pathology of Alzheimer's disease. Comprehensive solid-state NMR (SSNMR) structural studies on uniformly isotope-labeled Aβ assemblies have been hampered for a long time by sample heterogeneity and low spectral resolution. In this work, SSNMR studies on well-ordered fibril samples of Aβ(40) with an additional N-terminal methionine provide high-resolution spectra which lead to an accurate structural model. The fibrils studied here carry distinct structural features compared to previous reports. The inter-β-strand contacts within the U-shaped β-strand-turn-β-strand motif are shifted, the N-terminal region adopts a β-conformation, and new inter-monomer contacts occur at the protofilament interface. The revealed structural diversity in Aβ fibrils points to a complex picture of Aβ fibrillation.

Background-Arterial hypertension is a prime cause of morbidity and mortality in the general population. Pharmacological treatment has limitations resulting from drug side effects, costs, and patient compliance. Thus, we investigated whether traditional Chinese medicine acupuncture is able to lower blood pressure. Methods and Results-We randomized 160 outpatients (age, 58Ϯ8 years; 78 men) with uncomplicated arterial hypertension in a single-blind fashion to a 6-week course of active acupuncture or sham acupuncture (22 sessions of 30 minutes' duration). Seventy-eight percent were receiving antihypertensive medication, which remained unchanged. Primary outcome parameters were mean 24-hour ambulatory blood pressure levels after the treatment course and 3 and 6 months later. One hundred forty patients finished the treatment course (72 with active treatment, 68 with sham treatment). There was a significant (PϽ0.001) difference in posttreatment blood pressures adjusted for baseline values between the active and sham acupuncture groups at the end of treatment. For the primary outcome, the difference between treatment groups amounted to 6.4 mm Hg (95% CI, 3.5 to 9.2) and 3.7 mm Hg (95% CI, 1.6 to 5.8) for 24-hour systolic and diastolic blood pressures, respectively. In the active acupuncture group, mean 24-hour ambulatory systolic and diastolic blood pressures decreased significantly after treatment by 5.4 mm Hg (95% CI, 3.2 to 7.6) and 3.0 mm Hg (95% CI, 1.5 to 4.6), respectively. At 3 and 6 months, mean systolic and diastolic blood pressures returned to pretreatment levels in the active treatment group. Conclusions-Acupuncture according to traditional Chinese medicine, but not sham acupuncture, after 6 weeks of treatment significantly lowered mean 24-hour ambulatory blood pressures; the effect disappeared after cessation of acupuncture treatment.

We show here that by combining tailored approaches based on ultrafast (60 kHz) MAS on the Co(II)-replaced catalytic domain of matrix metalloproteinase 12 (CoMMP-12) we can observe and assign, in a highly paramagnetic protein in the solid state, (13)C and even (1)H resonances from the residues coordinating the metal center. In addition, by exploiting the enhanced relaxation caused by the paramagnetic center, and the low power irradiation enabled by the fast MAS, this can be achieved in remarkably short times and at very high field (21.2 T), with only less than 1 mg of sample. Furthermore, using the known crystal structure of the compound, we are able to distinguish and measure pseudocontact (PCS) contributions to the shifts up to the coordinating ligands and to unveil structural information.