HELIX 42 CRACK

HELIX 42 CRACK

HELIX 42 CRACK > https://urllie.com/2t7DGb

Innovating their thinking helped to reduce cracks through the highly versatile concrete reinforcement: +1132% in shear strength, +142% in durability, +800% in toughness and +42% in modulus of rupture.

NsrR subunits Cα tracings are depicted in blue and gold with ribbons indicating α-helices and arrows β-strands. DNA strands carry nucleotide numbers and are shown as cyan and burgundy ribbons, with stars marking four BII backbone conformations in the central region. Cluster atoms and histidine side chains forming hydrogen bonds to phosphate groups are depicted as spheres (Fe: red-brown, S: yellow, N: blue and C: gray). The first three helices and the labeled wing loop of each protein subunit interact with the DNA. Minimal and maximal P-to-P distances between phosphate groups across the minor groove are indicated with dotted lines and given in Å. The green dashed line follows the bp origins of the DNA double helix as determined with the program DSSR37.

The homologous E. coli NO sensor displays several amino acid sequence differences with ScNsrR in the DNA contacting region (Fig. 5). For example, ScNsrR Thr29, Thr41 and Thr48, which are hydrogen-bonded to phosphate groups of hmpA1, are neither conserved in EcNsrR, nor replaced by Ser, which would allow a similar interaction. In addition, the phosphate-binding His52 is substituted by Arg. These dissimilarities could explain why ScNsrR does not display significant affinity for EcNsrR-specific DNA sequences25. The above mentioned His and Thr residues are also not conserved in SvRsrR or EcIscR, the other two Rrf2 family iron-sulfur cluster binding sensors with known DNA complex structures, although Thr41 is replaced here by Ser. His42, the other ScNsrR residue that possibly makes a salt bridge with the phosphate backbone, is replaced by Tyr in those sensors. Amino acid sequence comparisons, including RlRirA and Sa and BsCymR, reveal a conserved Lx3Gx6Gx2GGx2L motif (Fig. 5) that spans the C-terminal region of helix 3 and the wing region. The comparison shows that most of the ScNsrR DNA contacting residues are not conserved in the eight Rrf2 family members. This indicates, as might be expected, that the different binding modes observed for these sensor/DNA complexes result from a combination of specific amino acid (Fig. 5) and nucleotide (Table 2) differences. A detailed comparison of the ScNsrR/hmpA1 and EcIscR/hyA complex structures reveals a small number of base-specific interactions (Table S1). Modelling different operator sequences on the structures of hmpA1 and hyA produces vdW collisions with the respective ScNsrR and EcIscR protein structures (shown in bold italics in Table 2).

The DNA double helices of the 39-bp rsrR, 29-bp hyA and 23-bp hmpA1 operator fragments display different shapes in their respective complexes to SvRsrR, EcIscR and ScNsrR (Fig. 6). The DNA structures accommodate the different positions and orientations of the H-wHTH motifs found in the bound proteins (Fig. S9). The MiG and MaG P-to-P distances (Fig. 6b, c) and widths (Fig. S10) observed at different locations of the DNA double helix in the three complexes are remarkably different. The MiGs are especially different in the central 7-bp region (Fig. 6b, c) for which no base-specific contacts with the protein are observed (Fig. 2 and Table S1). These groove width variations condition the distance between equivalent operator regions (Fig. S11), which could guide recognition by different Tfs32,33.

In view of these results, direct protein-to-DNA interactions, which mostly involve the RH and the wing (Figs. 2 and 6), are probably much more important for operator recognition. The DNA segments bending around the regulatory helix display a widening of the MaG. This widening is more pronounced in hyA than in hmpA1 and rsrR (Fig. S10), which could be due to the compression of the MiG between the P+2 phosphates of the neighboring central region in hyA (Fig. 6). The wing regions of ScNsrR, EcIscR and SvRsrR, which display the highest amino acid sequence homologies within Rrf2 family proteins (Fig. 5), interact with a more similar, relatively A/T-rich MiG (Figs. 2 and 6a). In hmpA1, as in hyA, the corresponding MiGWs are narrower than in rsrR. This is probably due to the close interaction of the positively charged ScNsrR Arg60, and EcIscR Arg59, with deoxyriboses and base rings at the MiG edge (Fig. 6c and Table S1). These interactions also compensate for the electrostatic repulsion between opposing phosphate groups. The broader rsrR MiG in the region that binds the protein wing could be explained by its lower A/T bp content and by the fact that in SvRsrR this Arg residue is substituted by Gln57 (Fig. 5).

Basal cell carcinoma (BCC) accounts for 90% of all malignant cutaneous lesions in the head and neck region and is therefore the most common type of skin cancer on the ear. It makes up one fifth of neoplasms that involve the ear and the temporal bone [20]. The vast majority of BCC occurs on the auricular helix and periauricular area which are especially susceptible as they are exposed to the most UV light. Nevertheless 15% arise in the external auditory canal. Five different clinical forms are distinguished in the literature: nodular-ulcerative, pigmented, cystic, superficial multicentric and morphealike. The most common type is the nodular-ulcerative. The lesion is a flesh-colored scaling papule, mostly erythematous to pink, sometimes pigmented, with a surrounding capillary network. It has a pearly border and can show a central ulcer (Fig. 3). This most frequent form may infiltrate the cartilage. Although metastases of BCC are extremely rare, the invasive character of the tumor can cause extensive local tissue destruction. The second most common type is the morphealike or sclerosing subtype. It is more troublesome as it has indistinct margins and infiltrates along deep tissue planes. It spreads centrifugally with a finger-like growth pattern which complicates therapy. The lesion can potentially extend to the temporal bone or parotid gland and remain undetected.

Winkler Disease is a chronic perichondritis which is thought to be related to limited vascularity at the lateral and anterior aspect of the auricle. The skin is tightly stretched over the underlying cartilage with minimal subcutaneous tissue which results in limited vascularity and ischaemia which is thought to promote the development of this lesion [72]. Mostly located on the helix this disease is characterized by a hard nodule which involves the skin and the cartilage of the ear (Fig. 8). Patients present with severe pain in the affected ear especially when slept on it at night. Although conservative treatment (radiation, topical antibiotics, intralesional steroids) has been described surgical excision should be preferred as lesions show a tendency to recur. A minimal skin excision should be combined with a more extensive cartilage resection to avoid recurrence [73].

Subplot A shows a schematic of the coarse-graining procedure, replacing a full atomistic representation of an alpha helical protein domain by a mesoscale bead model with bead distance r0. Subplot B shows a snapshot of a quasi-regular lamin meshwork (scale bar 1 µm) as observed in experimental imaging of oocytes; where structural imperfections are highlighted in white. Image of lamin meshwork reprinted with permission from Macmillan Publishers Ltd., from Nature [43], copyright © 1986. Subplot C depicts a schematic of the coarse grained protein network geometry used in this study, with the applied mode I tensile boundary conditions. The size of the network equals to 24 nm×24 nm, where each filament is represented by one alpha helix, as shown in the blow-up. A constant strain rate is applied in y-direction to apply mode I tensile loading through displacing the outermost rows of beads. The crack represents a geometrical flaw or inhomogeneity as they appear in vivo. Subplot D depicts characteristic force-strain curves for pulling individual alpha-helices as used in our mesoscale bead model. As explained in Materials and Methods, this force-strain behavior is derived from full-atomistic simulations and theoretical analysis, and has been validated against experimental studies. The labels α, β and γ identify the three major regimes of deformation.

Up until now the properties of alpha-helical protein networks specifically at the mesoscale have not yet been investigated, and no analysis of the rupture behavior of these networks was reported, despite their widely accepted significance of the mechanical performance and integrity. This has thus far hindered the formulation of bottom-up models that describe the structure-property relationships in protein networks under large deformation, which may explain their characteristic mechanical behavior. In particular, it remains unknown what the mechanism is by which these protein networks can sustain such large deformation of several hundred percent without catastrophic failure. This is an intriguing question since protein networks typically feature structural irregularities and flaws in their network makeup, as highlighted in Figure 1B. In synthetic materials (such as polymers, metals or ceramics), flaws typically lead to catastrophic failure at relatively small strains (often less than a few percent), preventing a material from undergoing very large deformation, reliably. This is because crack-like imperfections are generally responsible for initiating catastrophic failure [22], because they lead to very large stress concentrations at the corner of the cracks.

We begin our analysis with carrying a tensile deformation test of an alpha-helical protein network, by using the geometry and loading condition as shown in Figure 1C. We consider two geometric arrangements, as depicted in Figure 4 (lower part). First, a perfect protein network without a structural flaw. Second, a protein network with a structural flaw, here modeled as a crack-like inclusion. The goal of this analysis is to identify how an alpha-helical protein network responds to mechanical deformation under the presence of the crack. 2b1af7f3a8