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Force production in muscle is achieved through the interaction of myosin and actin. Strong binding states in active muscle are associated with Mg·ADP bound to the active site; release of Mg·ADP allows rebinding of ATP and dissociation from actin. Thus, Mg·ADP binding is positioned for adaptation as a force sensor. Mechanical loads on the lever arm can affect the ability of myosin to release Mg·ADP but exactly how this is done is poorly defined. Here we use F-actin decorated with double-headed smooth muscle myosin fragments in the presence of Mg·ADP to visualize the effect of internally supplied tension on the paired lever arms using cryoEM. The interaction of the paired heads with two adjacent actin subunits is predicted to place one lever arm under positive and the other under negative strain. The converter domain is believed to be the most flexible domain within myosin head. Our results, instead, point to the segment of heavy chain between the essential and regulatory light chains as the location of the largest structural change. Moreover, our results suggest no large changes in the myosin coiled coil tail as the locus of strain relief when both heads bind F-actin. The method would be adaptable to double-headed members of the myosin family. We anticipate that the study of actin-myosin interaction using double-headed fragments enables visualization of domains that are typically noisy in decoration with single-headed fragments., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Growth factors are considered an important component for periodontal wound healing and a key element in the periodontal regeneration triad. Randomized controlled clinical trials have demonstrated that purified recombinant human platelet-derived growth factor-BB (rhPDGF-BB) in combination with bone graft materials is effective in treating intrabony periodontal defects. Many clinicians are currently using rhPDGF-BB in combination with xenogeneic or allogeneic bone. Therefore, the purpose of this case series was to assess the clinical effectiveness of combining rhPDGF-BB with xenogeneic bone substitutes to treat severe intrabony periodontal defects. Three patients with challenging deep and wide intrabony defects were treated using a combination of rhPDGF-BB and xenogeneic graft matrix. Probing depth (PD) reduction, bleeding on probing (BOP), mobility reduction, and radiographic bone fill (RBF) were observed for 12 to 18 months. PD decreased from 9 mm to 4 mm, BOP was eliminated, mobility decreased, and RBF ranged from 85% to 95% over the postsurgical observation period. These results indicate that combination of rhPDGF-BB with xenogeneic bone substitutes is a safe and effective graft that leads to favorable clinical and radiographic outcomes for treating severe intrabony periodontal defects. Larger case series or randomized studies will further elucidate the clinical predictability of this treatment protocol. Int J Periodontics Restorative Dent 2023;43:193-200. doi: 1011607/prd.6313.

Purpose: To compare the effects of regular implant drills to osseodensifying drills used in clockwise and counterclockwise motions on bone dimension change and primary implant stability. Materials and Methods: A total of 40 bone models were made (20 × 15 × 4 mm) from porcine tibia to represent implants placed in soft bone. Implant osteotomies were prepared in the bone models using one of the following techniques: (1) regular implant drills in a clockwise direction (group A), (2) regular implant drills in a counterclockwise direction (group B), (3) osseodensifying drills in a clockwise direction (group C), and (4) osseodensifying drills in a counterclockwise direction (group D). Bone-level tapered titanium alloy implants (4.1 × 10 mm) were placed following osteotomy creation. The implant stability quotient (ISQ) was measured after implant placement. Each bone model was scanned with an optical scanner to convert to Standard Tessellation Language (STL) files before and after the osteotomy creation. Presurgical and postsurgical STL files were superimposed, and the dimensional changes were measured at 1, 3, and 7 mm from the crestal bone. Histomorphometric analysis was done, and bone-to-implant contact percentage (BIC%) was calculated. Results: There were no significant differences in ISQ values ( P = .239) between any of the groups. Histomorphometric analysis showed implants in group D had significantly higher BIC% than groups A ( P = .020) and B ( P = .009). The amount of bone expansion decreased with distance from the crest ( P < .001). Groups B ( P = .039) and D ( P = .001) showed significant expansions at all levels compared with group A. No other statistically significant differences in dimensional change were found between groups. Conclusion: Both regular and osseodensification burs used in a counterclockwise motion contribute to expansion of bone dimension compared to conventional drilling methods.

Recent structural investigation of amyloid filaments extracted from human patients demonstrated that the ex vivo filaments associated with different disease phenotypes adopt diverse molecular conformations, which are different from those of in vitro amyloid filaments. A very recent cryo-EM structural study also revealed that ex vivo α-synuclein filaments extracted from multiple system atrophy patients adopt distinct molecular structures from those of in vitro α-synuclein filaments, suggesting the presence of co-factors for α-synuclein aggregation in vivo. Here, we report structural characterizations of α-synuclein filaments formed in the presence of a potential co-factor, tau, using cryo-EM and solid-state NMR. Our cryo-EM structure of the tau-promoted α-synuclein filaments reveals some similarities to one of the previously reported polymorphs of in vitro α-synuclein filaments in the core region, while illustrating distinct conformations in the N- and C-terminal regions. The structural study highlights the conformational plasticity of α-synuclein filaments and the importance of the co-factors, requiring additional structural investigation of not only more ex vivo α-synuclein filaments, but also in vitro α-synuclein filaments formed in the presence of diverse co-factors. The comparative structural analyses will help better understand molecular basis of diverse structures of α-synuclein filaments and possible relevance of each structure to the disease phenotype., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The atomic structure of the complete myosin tail within thick filaments isolated from Lethocerus indicus flight muscle is described and compared to crystal structures of recombinant, human cardiac myosin tail segments. Overall, the agreement is good with three exceptions: the proximal S2, in which the filament has heads attached but the crystal structure doesn't, and skip regions 2 and 4. At the head-tail junction, the tail α-helices are asymmetrically structured encompassing well-defined unfolding of 12 residues for one myosin tail, ∼4 residues of the other, and different degrees of α-helix unwinding for both tail α-helices, thereby providing an atomic resolution description of coiled-coil "uncoiling" at the head-tail junction. Asymmetry is observed in the nonhelical C termini; one C-terminal segment is intercalated between ribbons of myosin tails, the other apparently terminating at Skip 4 of another myosin tail. Between skip residues, crystal and filament structures agree well. Skips 1 and 3 also agree well and show the expected α-helix unwinding and coiled-coil untwisting in response to skip residue insertion. Skips 2 and 4 are different. Skip 2 is accommodated in an unusual manner through an increase in α-helix radius and corresponding reduction in rise/residue. Skip 4 remains helical in one chain, with the other chain unfolded, apparently influenced by the acidic myosin C terminus. The atomic model may shed some light on thick filament mechanosensing and is a step in understanding the complex roles that thick filaments of all species undergo during muscle contraction., Competing Interests: The authors declare no competing interest.

The capsid structures of most Adeno-associated virus (AAV) serotypes, already assigned to an antigenic clade, have been previously determined. This study reports the remaining capsid structures of AAV7, AAV11, AAV12, and AAV13 determined by cryo-electron microscopy and three-dimensional image reconstruction to 2.96, 2.86, 2.54, and 2.76 Å resolution, respectively. These structures complete the structural atlas of the AAV serotype capsids. AAV7 represents the first clade D capsid structure; AAV11 and AAV12 are of a currently unassigned clade that would include AAV4; and AAV13 represents the first AAV2-AAV3 hybrid clade C capsid structure. These newly determined capsid structures all exhibit the AAV capsid features including 5-fold channels, 3-fold protrusions, 2-fold depressions, and a nucleotide binding pocket with an ordered nucleotide in genome-containing capsids. However, these structures have viral proteins that display clade-specific loop conformations. This structural characterization completes our three-dimensional library of the current AAV serotypes to provide an atlas of surface loop configurations compatible with capsid assembly and amenable for future vector engineering efforts. Derived vectors could improve gene delivery success with respect to specific tissue targeting, transduction efficiency, antigenicity or receptor retargeting.

Background: Due to the complications of root canal treatment, conservative modalities to preserve pulp vitality are favorable. Direct pulp capping (DPC) refers to the coverage of the pulp tissue exposed by a biocompatible agent that can improve the prognosis of the tooth by 44% to 95%. Some recent studies have reported more predictable results (a success rate of about 90%) for DPC with laser and regenerative materials such as mineral trioxide aggregate (MTA). This study aimed to clinically compare DPC with ProRoot MTA alone and in combination with Er:YAG (erbium-doped yttrium aluminium garnet) laser irradiation (2940 nm). Methods: This clinical trial was conducted on 26 patients with a mean age of 29 years (in the range of 17 to 46 years) who required DPC following pulp exposure during deep caries removal. The teeth were divided into two groups. In the control group, the teeth underwent DPC with ProRoot MTA while in the test group, the teeth were first irradiated with a 2940 nm Er:YAG laser and then underwent DPC with ProRoot MTA. The patients were recalled at one, 3 and 6 months for the follow-up (clinical and radiographic examinations). The data were analyzed using Fisher exact test. Results: The success rate was 75% in the laser group and 93% in the control group. The groups were not significantly different ( P >0.05). Conclusion: No significant difference was found in terms of the success rate of DPC with ProRoot MTA alone and in combination with Er:YAG laser irradiation., (Copyright © 2020 J Lasers Med Sci.)

Striated muscle thick filaments are composed of myosin II and several non-myosin proteins. Myosin II's long α-helical coiled-coil tail forms the dense protein backbone of filaments, whereas its N-terminal globular head containing the catalytic and actin-binding activities extends outward from the backbone. Here, we report the structure of thick filaments of the flight muscle of the fruit fly Drosophila melanogaster at 7 Å resolution. Its myosin tails are arranged in curved molecular crystalline layers identical to flight muscles of the giant water bug Lethocerus indicus Four non-myosin densities are observed, three of which correspond to ones found in Lethocerus ; one new density, possibly stretchin-mlck, is found on the backbone outer surface. Surprisingly, the myosin heads are disordered rather than ordered along the filament backbone. Our results show striking myosin tail similarity within flight muscle filaments of two insect orders separated by several hundred million years of evolution., (© 2020 Daneshparvar et al.)

Several methods are used for periodontal regeneration and alveolar ridge reconstruction. This study aimed to compare the bone regeneration capacities of MinerOss X, Bio-Oss, and autograft in rabbit calvaria. In this animal study, four defects measuring 8 mm in diameter were created in the calvaria of 10 rabbits using a trephine bur. Three defects were randomly filled with MinerOss X, Bio-Oss, and autogenous bone. The fourth defect remained empty as a control. The rabbits were sacrificed after 4 or 8 weeks. Calvarial samples were taken and histopathologically evaluated. The mean number of osteoblasts and the amount of newly formed bone in all groups were higher at 8 compared to 4 weeks. At 4 and 8 weeks, the amount of newly formed bone and number of osteoblasts and osteocytes in MinerOss X group were significantly greater than the corresponding values in other groups, and MinerOss X was superior to Bio-Oss and autograft in all the assessed variables at both 4 and 8 weeks (P < .001). Within the limitations of this study, the results showed that the number of osteoblasts and osteocytes and the amount of newly formed bone in the MinerOss X group were higher than those in Bio-Oss and autograft groups. However, further clinical studies are warranted.

Objectives: The purpose of this study was to determine buccal bone and soft tissue thicknesses and their correlation in the maxillary anterior region using cone beam computed tomography (CBCT)., Materials and Methods: In this cross sectional study, 330 sound maxillary incisors in 60 patients with a mean age of 37.5 years were assessed by CBCT scans. For better visualization of soft tissue, patients were asked to use plastic retractors in order to retract their lips and cheeks away from the gingival tissue before taking the scans. Measurements were made in three different positions: at the crest and at 2 and 5mm apical to the crest. The cementoenamel junction-crest distance was measured. for data analyses, the Pearson's correlation coefficient, ANOVA and intraclass correlation coefficient were used., Results: There were mildly significant linear associations between labial soft tissue and bone thickness in the canines and incisors (r<0.40, P<0.05), but no association was found for the lateral incisors. The mean thickness of buccal bone differed significantly in the maxillary anterior teeth, being greater for the lateral incisors (P<0.05). For soft tissue thickness, the results were the same, and the least thickness was recorded for the canines. There was a mild association between labial soft tissue and bone thickness in canines and incisors (r=0.2, P=0.3), but no such linear association was seen for the lateral incisors., Conclusions: The mean thickness of buccal bone and soft tissue in the anterior maxilla was <1mm and there was a mild linear correlation between them.

Soft tissue seal plays a critical role in long-term success of dental implants, and the effects of implant surface treatments such as laser ablation have been a topic of particular interest in this respect. Considering the existing controversy regarding soft tissue behavior in contact with implant surfaces, this study sought to assess the morphology, proliferation, and gene expression of human gingival fibroblasts (HGFs) on different abutment surfaces. In this in vitro, experimental study, HGFs were cultured on 45 discs (Laser-Lok, titanium, and zirconia). Cell morphology, proliferation rate, and interleukin 10 (IL-10), tumor necrosis factor alpha (TNFα), fibronectin, and integrin gene expressions were assessed by electron microscopy, methyl thiazol tetrazolium (MTT) assay, and real-time polymerase chain reaction (PCR), respectively. Data were analyzed using ANOVA and the Kruskal-Wallis H test. Fibroblast attachment was noted in all the three groups. Spindle-shaped cells with pseudopod-like processes were more frequently seen in the Laser-Lok group. Cell proliferation was significantly higher in the Laser-Lok group compared to those in the other groups (P = 0.0002). Significant differences were found in the expression of IL-10, TNFα, fibronectin, and integrin genes among the groups (P < 0.01). Within the limitations of this study, HGFs on Laser-Lok surfaces had a more mature morphology and greater proliferation and differentiation as compared to those on zirconia and titanium surfaces. This indicates better attachment of these cells to laser-modified surfaces, creating a more efficient soft tissue seal around dental implants.

The presence of keratinized mucosa plays a fundamental role in peri-implant soft tissue health. This study assessed the impact of the width of keratinized mucosa (WKM) on peri-implant soft tissue parameters. A cross-sectional study was conducted on 110 bone-level implants in 36 patients. A minimum of 6 months had passed since the loading of implants, and the patients had at least 1 implant in 1 quadrant at the molar or premolar site restored with a single crown or fixed partial denture. The health of peri-implant soft tissue was assessed with a modified bleeding index (MBI), modified plaque index (MPI), and modified gingival index (MGI). Probing depth (PD), gingival recession (GR), and WKM were also measured. History of smoking and oral hygiene methods were recorded. A significant inverse correlation existed between WKM and the parameters MBI, MPI, MGI, and GR (P < 0.05). Values of MBI, MPI, MGI, and GR were significantly lower in areas with WKM ≥ 2 mm and higher in areas with WKM < 2 mm (P < 0.05). The WKM was greatest in subjects using the vibratory toothbrushing technique and narrowest in those using the horizontal toothbrushing technique (P < 0.05). The mean WKM was significantly greater in smokers than in nonsmokers (P < 0.05). Results of this study indicate that an association exists between WKM and peri-implant soft tissue health. A minimum of 2 mm of keratinized mucosa around implants is recommended.

Objective: The focus of this paper is to evaluate the influence of mechanical characteristics of the implant on primary stability in different bone types, based on resonance frequency analysis (RFA)., Materials and Methods: A number of 60 Nobel Biocare Replace Select TiUnit Tapered implants of two different lengths (10 mm and 13 mm) and three different widths as 3.4 mm (narrow platform (NP)), 4.3 mm (regular platform (RP)) and 5 mm (wide platform (WP)) were placed into two different groups of bone blocks. Bone blocks were different in bone quality, but similar to bone types D1 and D3. Immediately, after implant placement, implant stability quotient (ISQ) was measured using the Osstell mentor device., Results: ISQ values for implant placements in D1 bone were significantly higher than those for implants placed in D3 bone. In D1 bone, the implant length did not make any significant difference in primary stability; however, in D3 bone, the primary stability of the implant increased when longer implants were utilized. NP implants presented significantly lower ISQ values compared to the two wider implants., Conclusion: In cases of low bone quality, the optimum increase in the implant length and diameter should be taken into account to achieve higher primary stability.