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Protein structure determination by proton-detected magic-angle spinning (MAS) NMR has focused on highly deuterated samples, in which only a small number of protons are introduced and observation of signals from side chains is extremely limited. Here, we show in two fully protonated proteins that, at 100-kHz MAS and above, spectral resolution is high enough to detect resolved correlations from amide and side-chain protons of all residue types, and to reliably measure a dense network of ¹H-¹H proximities that define a protein structure. The high data quality allowed the correct identification of internuclear distance restraints encoded in 3D spectra with automated data analysis, resulting in accurate, unbiased, and fast structure determination. Additionally, we find that narrower proton resonance lines, longer coherence lifetimes, and improved magnetization transfer offset the reduced sample size at 100-kHz spinning and above. Less than 2 weeks of experiment time and a single 0.5-mg sample was sufficient for the acquisition of all data necessary for backbone and side-chain resonance assignment and unsupervised structure determination. We expect the technique to pave the way for atomic-resolution structure analysis applicable to a wide range of proteins.

Background Silicone breast augmentation remains one of the most common aesthetic surgery procedures, and 2022 marks the 60th anniversary of the first case. Recent studies suggest a link between double capsule (DC) formation and macro-textured devices. Methods Between 2010 and 2015, 268 aesthetic patients underwent bilateral mammary prosthesis exchange for indications including PIP exchange, adverse capsular contracture and ultrasonographic evidence of rupture. All surgery, in the form of implant exchange and capsulectomy, was undertaken by the senior author using standard techniques. A retrospective review was undertaken, and data analysed with descriptive statistics and Fisher’s exact and Mann–Whitney U tests. Results Of 268 patients identified, 40 (14.9%) showed some degree of capsular duplication and bilateral involvement was marginally more common (52.5%). Two macroscopic patterns of duplication were observed: complete and subtotal . Complete DCs correlated with a clinical triad of extreme firmness, mobility and minimal-to-no pain. Whilst a wide range of manufacturers was represented, macro-textured devices were associated with the highest DC prevalence (58.3% vs. 5.6%) (Fisher’s exact test p < 0.00001). Patients with DC had been implanted for less than half the time, median 52 versus. 120 months ( p = 0.0003) of those without. Discussion An elevated prevalence of duplicate capsules in macro-textured prostheses is reconfirmed in addition to a novel symptom constellation that may assist with clinical diagnosis. Our study reinforces the aetiopathogenic influence of the elastomer in DC formation and reports DC for the first time in non-macrotextured implants. Single-surgeon cohort of 268 consecutive patients with 532 implants Statistically significant association of macro-textured devices with DC Statistically significant reduced duration of implantation of macro-textured devices First report of DC in non-macro-textured devices Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

β-barrel proteins mediate nutrient uptake in bacteria and serve vital functions in cell signaling and adhesion. For the 14-strand outer membrane protein G of Escherichia coli , opening and closing is pH-dependent. Different roles of the extracellular loops in this process were proposed, and X-ray and solution NMR studies were divergent. Here, we report the structure of outer membrane protein G investigated in bilayers of E. coli lipid extracts by magic-angle-spinning NMR. In total, 1847 inter-residue 1 H– 1 H and 13 C– 13 C distance restraints, 256 torsion angles, but no hydrogen bond restraints are used to calculate the structure. The length of β-strands is found to vary beyond the membrane boundary, with strands 6–8 being the longest and the extracellular loops 3 and 4 well ordered. The site of barrel closure at strands 1 and 14 is more disordered than most remaining strands, with the flexibility decreasing toward loops 3 and 4. Loop 4 presents a well-defined helix. Porins, like OmpG, are embedded in the outer membrane of bacteria and facilitate uptake and secretion of nutrients and ions. Here the authors present a protocol for solid state NMR structure determination of proteins larger than 25 kDa and use it to structurally characterize membrane embedded OmpG.

When plant-pathogenic oomycetes infect their hosts, they employ a large arsenal of effector proteins to establish a successful infection. Some effector proteins are secreted and are destined to be translocated and function inside host cells. The largest group of translocated proteins from oomycetes is the RxLR effectors, defined by their conserved N-terminal Arg-Xaa-Leu-Arg (RxLR) motif. However, the precise role of this motif in the host cell translocation process is unclear. Here, detailed biochemical studies of the RxLR effector AVR3a from the potato pathogen Phytophthora infestans are presented. Mass spectrometric analysis revealed that the RxLR sequence of native AVR3a is cleaved off prior to secretion by the pathogen and the N terminus of the mature effector was found likely to be acetylated. High-resolution NMR structure analysis of AVR3a indicates that the RxLR motif is well accessible to potential processing enzymes. Processing and modification of AVR3a is to some extent similar to events occurring with the export element (PEXEL) found in malaria effector proteins from Plasmodium falciparum. These findings imply a role for the RxLR motif in the secretion of AVR3a by the pathogen, rather than a direct role in the host cell entry process itself.

Anastomosis between posterior superior alveolar artery and infraorbital artery can go through bony canal in the lateral wall of the maxilla. This artery is called alveolar antral artery. It can complicate lateral sinus lift procedure by bleeding and hemosinus formation or bone graft wash out. The artery can also go in soft tissues where is not visible on cone beam computed tomography. In previous studies, the relation of this artery to sinus floor or alveolar process was measured. These structures are highly unstable during lifetime and after tooth loss. The aim of this study is to study presence and relations of bony canal in the lateral maxillary wall, to characterize the group of patients which is more likely to have bone canal in the lateral maxilla. The aim and the novelty of this study is the describing of the relationship of the bony canal to the more stable structure of hard palate and describing the relation of presence of bony canal on width of maxillary sinus, and to facilitate the prediction of presence of the alveolar antral artery. The cone beam computed tomography scans of the patients (251 in number) of the university hospital were examined for presence of alveolar antral artery (148 was fulfilled inclusion criteria), patient were characterized by gender, age, and sinus type (wide, average, narrow). The diameter of the bony canal and its relation to the level of sinus floor and hard palate were measured. The cone beam computed tomography scans of 148 patients, out of it 55 man (37,2%) and 93 women (62,8%). Bony canal containing alveolar anastomosis was found in 69 cases (57,0%). Presence of the bony canal in the lateral wall of maxillae showed statistical probability depending on age with  = 0, 064 according to Mann-Whitney test. The older patients have more likely the bony canal. The presence of the alveolar antral artery was found more likely in the wide sinuses. The hard palate level can serve as a prediction point of alveolar antral artery only in first molar and second premolar region. In accordance with previous studies the width of bony canal is significantly higher in group of man (  = 0, 015). There was found a correlation between smaller distance of bony canal from sinus floor in the presence of teeth (  = 0, 067). After tooth loss the distance between sinus floor and bony canal increases, but the distance of bony canal to hard palate level stays constant. This can be explained hypothetically so that periodontal ligaments and root surface acts as a barrier for sinus pneumatization. Lateral sinus lifting in some cases can be unenviable, the knowledge about alveolar antral artery anatomy can reduce the risk of arterial bleeding. The cone-beam computed tomography is a routine examination prior to augmentation surgery and therefore the data obtained from it has an impact on clinical practice.

It has been shown that selective etching improves the bond strength of some self-adhesive resin cements to enamel. The same has yet to be determined with dentin pre-treatment. To evaluate the tensile bond strength of two self-adhesive resin cements after two dentin surface pre-treatments, and also to analyze the cement/dentin interface. One hundred and twelve human third molars were extracted. The teeth were distributed into seven groups (  = 16). Maxcem Elite Chroma (MAX) (Kerr, Scafati, Italy) and Relyx U200 (RLX) (3M ESPE, Neuss, Germany) were used without pre-treatment or with two dentin pre-treatments (polyacrylic acid or phosphoric acid). A conventional etch-and-rinse (EAR) luting cement, NX3 Nexus (NX3) (Kerr, Scafati, Italy), was used as an external control group. Before testing, all specimens were stored in distilled water for 24 hours. Three specimens from each group were prepared for scanning electron microscopy observation (SEM). A tensile bond strength test (TBS) was performed for the remaining samples. The data were statistically analyzed using the Kruskal-Wallis test and Pairwise comparisons using the Wilcoxon rank sum test. MAX without pre-treatment and with phosphoric acid etching attained statistically similar bond strengths to NX3 (  > 0.05). There was a statistical difference (  = 0.00488) between RLX without pre-treatment (5.62 MPa) and NX3 (10.88 MPa). Phosphoric acid pre-treatment increases the bond strength values of RLX to a strength that is comparable to NX3 (  > 0.05). The lowest tensile bond strength (TBS) was attained after the application of polyacrylic acid with MAX (1.98 MPa). No statistical differences were found between the RLX bond strength values after polyacrylic acid treatment and RLX without pre-treatment or NX3 (  > 0.05). SEM observations disclosed an enhanced potential of the self-adhesive cements to infiltrate into dentin tubules and form resin tags when applied after phosphoric acid pre-treatment. The failure mode was dominantly adhesive. On dentin, the self-adhesive resin cement MAX might be an effective alternative to conventional resin cement. Etching the dentin with phosphoric acid does not have a negative effect on the bond strength of MAX to dentin. On the other hand, phosphoric acid improved the bond strength of RLX when compared to EAR cement.

Spectra obtained by application of multidimensional Fourier Transformation (MFT) to sparsely sampled nD NMR signals are usually corrupted due to missing data. In the present paper this phenomenon is investigated on simulations and experiments. An effective iterative algorithm for artifact suppression for sparse on-grid NMR data sets is discussed in detail. It includes automated peak recognition based on statistical methods. The results enable one to study NMR spectra of high dynamic range of peak intensities preserving benefits of random sampling, namely the superior resolution in indirectly measured dimensions. Experimental examples include 3D 15 N- and 13 C-edited NOESY-HSQC spectra of human ubiquitin.

Background:Medicine use is the most common intervention in health care. The frequency with which medicines are used means medication-related problems are very common. One common type of medication-related problems is adverse drug events, which are unintended and harmful effects associated with use of medicines. Reporting of adverse drug events to regulatory authorities is important for evaluation of safety of medicines; however, these adverse effects are frequently unreported due to various factors, including lack of consumer-friendly reporting tools.Objective:The aim of this study was to develop a user-friendly digital tool for consumers to report medication-related adverse effects.Methods:The project consisted of 3 parts: (1) content development, including a systematic literature search; (2) iterative system development; and (3) usability testing. The project was guided by participatory design principles, which suggest involving key stakeholders throughout the design process. The first 2 versions were developed as a mobile app and were tested with end users in 2 workshops. The third version was developed as a web application and was tested with consumers who were taking regular medicines. Consumers were asked to complete a modified version of the mHealth app usability questionnaire (MAUQ), an 18-item questionnaire with each item scored using a 7-point Likert scale ranging from 0 (strongly disagree) to 7 (strongly agree). The MAUQ assessed 3 subscales including ease of use (5 items), interface and satisfaction (7 items), and usefulness (6 items). Continuous variables were reported as mean (SD) values, whereas categorical variables were presented as frequencies (percentages). Data analysis was conducted in Microsoft Excel.Results:The content for the system was based on a systematic literature search and short-listing of questions, followed by feedback from project team members and consumers. Feedback from consumers in the 2 workshops were incorporated to improve the functionality, visual design, and stability of the third (current) version. The third version of the system was tested with 26 consumers. A total of 79% (N=307/390) of all responses on the MAUQ were scored 6 or 7, indicating that users generally strongly agree with the usability of the system. When looking at the individual domains, the system had an average score of 6.3 (SD 0.9) for “ease of use,” 6.3 (SD 0.8) for “interface and satisfaction,” and 5.2 (SD 1.4) for “usefulness.”Conclusions:The web-based system for medicine adverse effects reporting is a user-friendly tool developed using an iterative participatory design approach. Future research includes further improving the system, particularly the usefulness of the system, as well as testing the scalability and performance of the system in practice.

A method for five-dimensional spectral reconstruction of non-uniformly sampled NMR data sets is proposed. It is derived from the previously published signal separation algorithm, with major alterations to avoid unfeasible processing of an entire five-dimensional spectrum. The proposed method allows credible reconstruction of spectra from as little as a few hundred data points and enables sensitive resonance detection in experiments with a high dynamic range of peak intensities. The efficiency of the method is demonstrated on two high-resolution spectra for rapid sequential assignment of intrinsically disordered proteins, namely 5D HN(CA)CONH and 5D (HACA)CON(CO)CONH.

The mobility of the 110 nm-Fe particles in a viscous sucrose solution depends on the concentration of the nanoparticles. When the average particle–particle nearest neighbor distance < > is less than 250 nm, the particle interaction slows down their mobility. When < > is more than 170 nm, the small mobility of nanoparticles does not depend on their concentration. The critical distance is approximately equal to 2 = 260 nm, where is the hydrodynamic radius, determined by the dynamic light scattering (DLS) method.