The triple-helical structure of collagen, responsible for collagen's remarkable biological and mechanical properties, has inspired both basic and applied research in synthetic peptide mimetics for decades. Since non-proline amino acids weaken the triple helix, the cyclic structure of proline has been considered necessary, and functional collagen mimetic peptides (CMPs) with diverse sidechains have been difficult to produce. Here we show that N-substituted glycines (N-glys), also known as peptoid residues, exhibit a general triple-helical propensity similar to or greater than proline, allowing synthesis of thermally stable triple-helical CMPs with unprecedented sidechain diversity. We found that the N-glys stabilize the triple helix by sterically promoting the preorganization of individual CMP chains into the polyproline-II helix conformation. Our findings were supported by the crystal structures of two atomic-resolution N-gly-containing CMPs, as well as experimental and computational studies spanning more than 30 N-gly-containing peptides. We demonstrated that N-gly sidechains with diverse exotic moieties including a 'click'-able alkyne and a photo-sensitive sidechain can be incorporated into stable triple helices, enabling functional applications such spatio-temporal control of cell adhesion and migration on a gelatin matrix. The folding principles discovered in this study open up opportunities for a new generation of collagen mimetic therapeutics and materials with extraordinary properties. design principles uncovered in this study drastically expand the library of residues with high triple-helical propensity, which has immense implications for a new generation of collagenmimetic therapeutics and materials. Results and DiscussionTriple-helical stability of CMPs with N-glys. To investigate the triple-helical folding propensity of peptoids residues, we inserted a series of N-gly guests into the central X position of a conventional CMP host peptide with the sequence: Ac-(GlyProHyp)3-Gly-X-Hyp-(GlyProHyp)3-NH2 (designated as X-CMP, Fig. 1b, and supplementary Materials and Methods) 34 . We measured the X-CMPs' triple-helical stability via thermal unfolding experiments monitored under circular dichroism (CD, Fig. 1c, Supplementary Section 3 and Table S1), first in a group of N-glys with sidechains selected from the canonical amino acids (Fig. 1d). It is known that Pro is the most stabilizing amino acid at position X, and substitution from Pro to another canonical amino acid clearly reduces Tm by 4-17 °C (Fig. 1d, column AA) 14 . Surprisingly, we found that many of the N-glys with canonical sidechains were at least as stable as Pro, and almost all N-gly residues were more stable than their amino acid counterparts (Fig. 1d, exception: Nval), with the biggest Tm difference seen between Nphe-and Phe-CMP (Fig. 1c). These results demonstrate that, in the X position of the CMP, shifting the sidechain from the Cα carbon to the nitrogen (i.e., transforming a canonical amino acid to its peptoid analogue) may improve triple-he...
The majority of dietary thyroid supplements studied contained clinically relevant amounts of T4 and T3, some of which exceeded common treatment doses for hypothyroidism. These amounts of thyroid hormone, found in easily accessible dietary supplements, potentially expose patients to the risk of alterations in thyroid levels even to the point of developing iatrogenic thyrotoxicosis. The current study results emphasize the importance of patient and provider education regarding the use of dietary supplements and highlight the need for greater regulation of these products, which hold potential danger to public health.
Using Ivanic's (2004) framework, the study of 20 elementary teachers examines the relationships among teachers' beliefs about writing, their instructional practices, and contextual factors. While the district-adopted curriculum reflected specific discourses, teachers' beliefs and practices reflected a combination of discourses. The nature of the professional development tended to reinforce particular discourses, but occasionally offered an alternative. The three cases revealed how teachers negotiated the tensions among various discourses. Beth exemplified a skills discourse, but demonstrated beliefs about writing as communication; however, she did not articulate tensions between the discourses and followed the district, skillsinfused curriculum. Amber borrowed from skills, traits, process, and genre discourses without resolving potential contradictions, resulting in instructional practices that had little coherence. Jackson, who brought in his own writing as a hip-hop artist, illustrated the social practices discourse as well as creativity and genre discourses to create an enhanced version of a district-adopted curriculum. Implications for practice include raising teacher's awareness of the contradictory discourses that surround them.
This report is one of a series of reports documenting the methods and findings of a multi-year, multi-disciplinary project coordinated by the Pacific Earthquake Engineering Research Center (PEER and funded by the California Earthquake Authority (CEA). The overall project is titled “Quantifying the Performance of Retrofit of Cripple Walls and Sill Anchorage in Single-Family Wood-Frame Buildings,” henceforth referred to as the “PEER–CEA Project.” The overall objective of the PEER–CEA Project is to provide scientifically based information (e.g., testing, analysis, and resulting loss models) that measure and assess the effectiveness of seismic retrofit to reduce the risk of damage and associated losses (repair costs) of wood-frame houses with cripple wall and sill anchorage deficiencies as well as retrofitted conditions that address those deficiencies. Tasks that support and inform the loss-modeling effort are: (1) collecting and summarizing existing information and results of previous research on the performance of wood-frame houses; (2) identifying construction features to characterize alternative variants of wood-frame houses; (3) characterizing earthquake hazard and ground motions at representative sites in California; (4) developing cyclic loading protocols and conducting laboratory tests of cripple wall panels, wood-frame wall subassemblies, and sill anchorages to measure and document their response (strength and stiffness) under cyclic loading; and (5) the computer modeling, simulations, and the development of loss models as informed by a workshop with claims adjustors. Quantifying the difference of seismic performance of un-retrofitted and retrofitted single-family wood-frame houses has become increasingly important in California due to the high seismicity of the state. Inadequate lateral bracing of cripple walls and inadequate sill bolting are the primary reasons for damage to residential homes, even in the event of moderate earthquakes. Physical testing tasks were conducted by Working Group 4 (WG4), with testing carried out at the University of California San Diego (UCSD) and University of California Berkeley (UCB). The primary objectives of the testing were as follows: (1) development of descriptions of load-deflection behavior of components and connections for use by Working Group 5 in development of numerical modeling; and (2) collection of descriptions of damage at varying levels of peak transient drift for use by Working Group 6 in development of fragility functions. Both UCSD and UCB testing included companion specimens tested with and without retrofit. This report documents the portions of the WG4 testing conducted at UCB: two large-component cripple wall tests (Tests AL-1 and AL-2), one test of cripple wall load-path connections (Test B-1), and two tests of dwelling superstructure construction (Tests C-1 and C-2). Included in this report are details of specimen design and construction, instrumentation, loading protocols, test data, testing observations, discussion, and conclusions.
This teaching tip showcases instructional strategies and scaffolds from an out‐of‐school digital writing camp. Often, teachers may be hesitant to incorporate digital tools into their literacy instruction for various reasons (e.g., scripted curriculum, fear and uncertainty of digital tools, lack of experience and knowledge with technology), yet it is quite similar to using the writers’ workshop approach with the added necessity of explicit scaffolding. Three main scaffolds of reading aloud mentor texts, teacher modeling of the digital tools, and providing time to play with the digital tools are further explained. The author highlights lower to higher tech digital tools, such as Google Slides, PicLits, Animoto, and iMovie, and reveals how they can be incorporated into the literacy classroom in engaging and meaningful ways.
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