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itor, Cesetti, Keller, Bruch, Ertongur-Fauth, Riedel, Scholz, Lau, Schneider, Meier, Hafner and Rudolf.Proteolytic susceptibility during endolysosomal degradation is decisive for allergic sensitization. In the major birch pollen allergen Bet v 1 most protease cleavage sites are located within its secondary structure elements, which are inherently inaccessible to proteases. The allergen thus must unfold locally, exposing the cleavage sites to become susceptible to proteolysis. Hence, allergen cleavage rates are presumed to be linked to their fold stability, i.e., unfolding probability. Yet, these locally unfolded structures have neither been captured in experiment nor simulation due to limitations in resolution and sampling time, respectively. Here, we perform classic and enhanced molecular dynamics (MD) simulations to quantify fold dynamics on extended timescales of Bet v 1a and two variants with higher and lower cleavage rates. Already at the nanosecond-timescale we observe a significantly higher flexibility for the destabilized variant compared to Bet v 1a and the proteolytically stabilized mutant. Estimating the thermodynamics and kinetics of local unfolding around an initial cleavage site, we find that the Bet v 1 variant with the highest cleavage rate also shows the highest probability for local unfolding. For the stabilized mutant on the other hand we only find minimal unfolding probability. These results strengthen the link between the conformational dynamics of allergen proteins and their stability during endolysosomal degradation. The presented approach further allows atomistic insights in the conformational ensemble of allergen proteins and provides probability estimates below experimental detection limits. Copyright © 2020 Kamenik, Hofer, Handle and Liedl.Today, the sedimentation of proteins into a magic-angle spinning (MAS) rotor gives access to fast and reliable sample preparation for solid-state Nuclear Magnetic Resonance (NMR), and this has allowed for the investigation of a variety of non-crystalline protein samples. High protein concentrations on the order of 400 mg/mL can be achieved, meaning that around 50-60% of the NMR rotor content is protein; the rest is a buffer solution, which includes counter ions to compensate for the charge of the protein. We have demonstrated herein the long-term stability of four sedimented proteins and complexes thereof with nucleotides, comprising a bacterial DnaB helicase, an ABC transporter, an archaeal primase, and an RNA polymerase subunit. Solid-state NMR spectra recorded directly after sample filling and up to 5 years later indicated no spectral differences and no loss in signal intensity, allowing us to conclude that protein sediments in the rotor can be stable over many years. We have illustrated, using an example of an ABC transporter, that not only the structure is maintained, but that the protein is still functional after long-term storage in the sedimented state. Copyright © 2020 Wiegand, Lacabanne, Torosyan, Boudet, Cadalbert, Allain, Meier and Böckmann.Due to the considerable environmental impact and the controversial animal welfare associated with industrial meat production, combined with the ever-increasing global population and demand for meat products, sustainable production alternatives are indispensable. In 2013, the world's first laboratory grown hamburger made from cultured muscle cells was developed. However, coming at a price of $300.000, and being produced manually, substantial effort is still required to reach sustainable large-scale production. One of the main challenges is scalability. Microcarriers (MCs), offering a large surface/volume ratio, are the most promising candidates for upscaling muscle cell culture. However, although many MCs have been developed for cell lines and stem cells typically used in the medical field, none have been specifically developed for muscle stem cells and meat production. This paper aims to discuss the MCs' design criteria for skeletal muscle cell proliferation and subsequently for meat production based on threeon-edible residues. Copyright © 2020 Bodiou, Moutsatsou and Post.Risk assessments are an important element in the management of patients with atrial fibrillation (AF). In this review, we aim to discuss the concepts and controversies surrounding the various risk factors for stroke and bleeding in AF. Indeed, there are a variety of clinical, electrical, biological, and genetic markers to guide stroke and bleeding risk assessments in AF. The more common factors have been used to formulate risk stratification scores. Some risk factors have shown promise, but others remain less well-defined. Our aim is to discuss concepts and controversies surrounding current evidence of risk factors for stroke and bleeding assessments in AF. Copyright © 2020 Ding, Harrison, Gupta, Lip and Lane.Primary and revision arthroplasties are increasing worldwide, as are periprosthetic joint infections (PJI). The management of PJI requires surgery, the strategy of which is dictated by the acute or chronic nature of the infection, with an exchange of the implant in the event of a chronic PJI or in the case of recurrence with the same pathogen. We report the case of a 63-year-old man with two episodes of Streptococcus dysgalactiae subsp. https://www.selleckchem.com/MEK.html equisimilis PJI within 9 months. Based on clinical suspicion of an haematogenous PJI, the patient was treated by DAIR (debridement, antibiotics, implant retention), while genomic sequencing revealed two different strains, confirming our hypothesis that no additional surgery was needed. Hence, we report a case where genomic analysis was decisive for the decision of the best therapeutic strategy. Copyright © 2020 Pham, Lazarevic, Gaia, Girard, Cherkaoui, Suva and Schrenzel.Background The short physical performance battery (SPPB) is a physical performance test of lower extremity function designed for non-disabled older adults. We aimed to establish reference values for community-dwelling Colombian adults aged 60 years or older in terms of (1) the total score; (2) the three subtest scores (walking speed, standing balance performance, and five times sit-to-stand test); and (3) the time to complete the five times sit-to-stand test, s and the walking speed test. Additionally, we sought to explore how much of the variance in the SPPB subtest scores could be explained by anthropometric variables (age, body mass, height, body mass index, and calf circumference). Methods Participants were men and women aged 60 years or older who participated in the Health and Well-being and Aging Survey in Colombia, 2015. A sample of 4,211 participants (57.3% women) completed the SPPB test, and their anthropometric variables were evaluated. Age-specific percentiles were calculated using the LMS method (3rd, 10th, 25th, 50th, 75th, 90th, and 97th percentiles).
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