Bridge Formation Research Articles

The Inability to Disassemble Rad51 Nucleoprotein Filaments Leads to Aberrant Mitosis and Cell Death.

The proper maintenance of genetic material is essential for the survival of living organisms. One of the main safeguards of genome stability is homologous recombination involved in the faithful repair of DNA double-strand breaks, the restoration of collapsed replication forks, and the bypass of replication barriers. Homologous recombination relies on the formation of Rad51 nucleoprotein filaments which are responsible for the homology-based interactions between DNA strands. Here, we demonstrate that without the regulation of these filaments by Srs2 and Rad54, which are known to remove Rad51 from single-stranded and double-stranded DNA, respectively, the filaments strongly inhibit damage-associated DNA synthesis during DNA repair. Furthermore, this regulation is essential for cell survival under normal growth conditions, as in the srs2Δ rad54Δ mutants, unregulated Rad51 nucleoprotein filaments cause activation of the DNA damage checkpoint, formation of mitotic bridges, and loss of genetic material. These genome instability features may stem from the problems at stalled replication forks as the lack of Srs2 and Rad54 in the presence of Rad51 nucleoprotein filaments impedes cell recovery from replication stress. This study demonstrates that the timely and efficient disassembly of recombination machinery is essential for genome maintenance and cell survival.

Temperature-Invariant Large Broadband Polyimide Dielectrics with Multimodal Porous Networks

Herein, we describe sponge-like polymeric materials with multimodal porous networks with stable ultralow dielectric properties over broad frequency and temperature ranges. A hierarchically porous polyimide (PI) film was prepared via nonsolvent-induced phase separation (NIPS), followed by stepwise thermal imidization. Through the swelling and the subsequent liquid–liquid phase separation, highly insulating interconnected pores of the internal layer and the water-vapor impermeable, closed-cell skin of the outer layer were directly formed on the PI film. The grafting of porous PI onto amino-functionalized mesoporous silica (AMS) to further adjust the overall thermal stability and dielectric constant has become a valid strategy. The porous PI-grafted-AMS (PPI-g-AMS) exhibited uniform micropores, which were regularly shaped with an average diameter of 16.3 ± 0.6 μm. The glass transition temperature (Tg) of PPI-g-AMS increased considerably from 367 °C to as high as 398 °C because of the formation of interchain cross-linking bridges in the AMS. Outstanding dielectric constant (Dk) and dissipation factor (Df) of 1.84 and 0.0018 at a frequency of 1 MHz, respectively, were achieved for PPI-g-AMS-1 with the addition of AMS with 1% wt. Moreover, stable and ultralow Dk (∼1.84 at 1 MHz) and Df (∼0.001 at 1 MHz) values were achieved over a broad temperature range from −20 to 200 °C. These findings indicate the broad application potential of polymeric materials as interlevel insulation materials in the next-generation 5G/6G infrastructure.

Conformation and Affinity Modulations by Multiple Phosphorylation Occurring in the BIN1 SH3 Domain Binding Site of the Tau Protein Proline-Rich Region.

An increase in phosphorylation of the Tau protein is associated with Alzheimer's disease (AD) progression through unclear molecular mechanisms. In general, phosphorylation modifies the interaction of intrinsically disordered proteins, such as Tau, with other proteins; however, elucidating the structural basis of this regulation mechanism remains challenging. The bridging integrator-1 gene is an AD genetic determinant whose gene product, BIN1, directly interacts with Tau. The proline-rich motif recognized within a Tau(210-240) peptide by the SH3 domain of BIN1 (BIN1 SH3) is defined as 216PTPP219, and this interaction is modulated by phosphorylation. Phosphorylation of T217 within the Tau(210-240) peptide led to a 6-fold reduction in the affinity, while single phosphorylation at either T212, T231, or S235 had no effect on the interaction. Nonetheless, combined phosphorylation of T231 and S235 led to a 3-fold reduction in the affinity, although these phosphorylations are not within the BIN1 SH3-bound region of the Tau peptide. Using nuclear magnetic resonance (NMR) spectroscopy, these phosphorylations were shown to affect the local secondary structure and dynamics of the Tau(210-240) peptide. Models of the (un)phosphorylated peptides were obtained from molecular dynamics (MD) simulation validated by experimental data and showed compaction of the phosphorylated peptide due to increased salt bridge formation. This dynamic folding might indirectly impact the BIN1 SH3 binding by a decreased accessibility of the binding site. Regulation of the binding might thus not only be due to local electrostatic or steric effects from phosphorylation but also to the modification of the conformational properties of Tau.

Substance P analogs devoid of key residues fail to activate human mast cells via MRGPRX2.

Mast cells play an important role in disease pathogenesis by secreting immunomodulatory molecules. Mast cells are primarily activated by the crosslinking of their high affinity IgE receptors (FcεRI) by antigen bound immunoglobulin (Ig)E antibody complexes. However, mast cells can also be activated by the mas related G protein-coupled receptor X2 (MRGPRX2), in response to a range of cationic secretagogues, such as substance P (SP), which is associated with pseudo-allergic reactions. We have previously reported that the in vitro activation of mouse mast cells by basic secretagogues is mediated by the mouse orthologue of the human MRGPRX2, MRGPRB2. To further elucidate the mechanism of MRGPRX2 activation, we studied the time-dependent internalization of MRGPRX2 by human mast cells (LAD2) upon stimulation with the neuropeptide SP. In addition, we performed computational studies to identify the intermolecular forces that facilitate ligand-MRGPRX2 interaction using SP. The computational predictions were tested experimentally by activating LAD2 with SP analogs, which were missing key amino acid residues. Our data suggest that mast cell activation by SP causes internalization of MRGPRX2 within 1 min of stimulation. Hydrogen bonds (h-bonds) and salt bridges govern the biding of SP to MRGPRX2. Arg1 and Lys3 in SP are key residues that are involved in both h-bonding and salt bridge formations with Glu164 and Asp184 of MRGPRX2, respectively. In accordance, SP analogs devoid of key residues (SP1 and SP2) failed to activate MRGPRX2 degranulation. However, both SP1 and SP2 caused a comparable release of chemokine CCL2. Further, SP analogs SP1, SP2 and SP4 did not activate tumor necrosis factor (TNF) production. We further show that SP1 and SP2 limit the activity of SP on mast cells. The results provide important mechanistic insight into the events that result in mast cell activation through MRGPRX2 and highlight the important physiochemical characteristics of a peptide ligand that facilitates ligand-MRGPRX2 interactions. The results are important in understanding activation through MRGPRX2, and the intermolecular forces that govern ligand-MRGPRX2 interaction. The elucidation of important physiochemical properties within a ligand that are needed for receptor interaction will aid in designing novel therapeutics and antagonists for MRGPRX2.

Cementum protein 1 gene-modified adipose-derived mesenchymal stem cell sheets enhance periodontal regeneration in osteoporosis rat.

Osteoporosis (OP) and periodontitis are both diseases with excessive bone resorption, and the number of patients who suffer from these diseases is expected to increase. OP has been identified as a risk factor that accelerates the pathological process of periodontitis. Achieving effective and safe periodontal regeneration in OP patients is a meaningful challenge. This study aimed to assess the efficacy and biosecurity of human cementum protein 1 (hCEMP1) gene-modified cell sheets for periodontal fenestration defect regeneration in an OP rat model. Rat adipose-derived mesenchymal stem cells (rADSCs) were isolated from Sprague-Dawley rats. After primary culture, rADSCs were subjected to cell surface analysis and multi-differentiation assay. And rADSCs were transduced with hCEMP1 by lentiviral vector, and hCEMP1 gene-modified cell sheets were generated. The expression of hCEMP1 was evaluated by reverse transcription polymerase chain reaction and immunocytochemistry staining, and transduced cell proliferation was evaluated by Cell Counting Kit-8. The hCEMP1 gene-modified cell sheet structure was detected by histological analysis and scanning electron microscopy. Osteogenic and cementogenic-associated gene expression was evaluated by real-time quantitative polymerase chain reaction. In addition, an OP rat periodontal fenestration defect model was used to evaluate the regeneration effect of hCEMP1 gene-modified rADSC sheets. The efficacy was assessed with microcomputed tomography and histology, and the biosecurity of gene-modified cell sheets was evaluated by histological analysis of the spleen, liver, kidney and lung. The rADSCs showed a phenotype of mesenchymal stem cells and possessed multi-differentiation capacity. The gene and protein expression of hCEMP1 through lentiviral transduction was confirmed, and there was no significant effect on rADSC proliferation. Overexpression of hCEMP1 upregulated osteogenic and cementogenic-related genes such as runt-related transcription factor 2, bone morphogenetic protein 2, secreted phosphoprotein 1 and cementum attachment protein in the gene-modified cell sheets. The fenestration lesions in OP rats treated with hCEMP1 gene-modified cell sheets exhibited complete bone bridging, cementum and periodontal ligament formation. Furthermore, histological sections of the spleen, liver, kidney and lung showed no evident pathological damage. This pilot study demonstrates that hCEMP1 gene-modified rADSC sheets have a marked ability to enhance periodontal regeneration in OP rats. Thus, this approach may represent an effective and safe strategy for periodontal disease patients with OP.

The Cornified Envelope: A Versatile Contributor to the Epidermal Barrier

The Cornified Envelope: A Versatile Contributor to the Epidermal Barrier

Die-sink EDM texturing to fabricate hydrophilic and wear resistant surface

ABSTRACT The present work emphasizes the fabrication of a series of V-groove channels utilizing electrical discharge machining using a pointed tungsten tool electrode. The prepared textured surface is tested for the shape of V-groove channel, wetting behavior, and tribological aspect. A decrease in shape error of V-groove channel is observed as the peak current increases from 4 A to 10 A due to an increase in discharge energy which functions as the melting or vaporizing of machined materials. The water contact angle decreases from 61.3160 (untextured surface) to 49.5670 (sample 4) showing an increase in hydrophilic behavior for the samples having nearly a V-groove-shaped channel. Further, there is a decrease in COF value from 0.48 (untextured surface) to 0.23 (sample 4). The decreased COF value attributes to the formation of metallic bridges in the V-groove channel. The prime wear mechanism for an untextured surface is found to be ploughing whereas adhesion with ploughing is dominant for textured surfaces.

Replacing Plastic with Bamboo: Eco-Friendly Disposable Tableware Based on the Separation of Bamboo Fibers and the Reconstruction of Their Network Structure

Disposable bamboo fiber tableware is a novel type of product that utilizes sustainable, high-performance bamboo fiber to minimize plastic pollution. In this study, we developed a high-utility bamboo fiber tableware product by employing a novel hybrid fiber-membrane strategy: We used a combination of steam explosion technology and mechanical refining to achieve the “up-down” separation of bamboo. During the molding process, slender bamboo fibers mixed with starch were interwoven into a strong three-dimensional network structure, which resulted in the abundant formation of physical interwinding, fiber bridging, and hydrogen bonding. The above structural features conferred excellent strength, water resistance, oil resistance, better high- and low-temperature resistance, a low content of dissolved substances, and the capacity for rapid degradation when compared with plastic and polylactic acid tableware. We conducted a product life cycle evaluation and found that replacing 20% of plastic tableware products with the bamboo fiber tableware product developed herein would be equal to reducing carbon emissions equivalent to 300,000 cars in a small city.

Three-Dimensional Structure of Fab Fragment of Monoclonal Antibody LNKB-2 Complexed with Antigenic Nonaptide from Human Interleukin-2

The three-dimensional structure of the antigen-binding fragment (Fab) of the monoclonal antibody LNKB-2 in complex with the synthetic antigenic nonapeptide of human interleukin-2 (IL-2; Lys-Pro-Leu-Glu-Glu-Val-Leu-Asn-Leu-O) was determined by X-ray method at a resolution of 2.6 Å in crystal space group P212121. The peptide adopts a somewhat distorted α-helical conformation, close to that of fragment 64–72 of the IL-2 antigen. Four out of the six hypervariable loops in the antigen-binding site of the Fab fragment are involved in nonapeptide association through hydrogen bonding, salt bridge formation, and hydrophobic interactions. Moreover, Tyr residues of an antibody play an important role in antigen-antibody recognition.

D21. Failure Rates Based on Alveolar Cleft Size: An Analysis of the Critical Size Defect for rhBMP-2/DBM and Iliac Crest in Alveolar Bone Grafting

PURPOSE: Iliac crest bone graft (ICBG) is the standard of alveolar bone grafting (ABG). However, recombinant human bone morphogenetic protein(rhBMP-2) with demineralized bone matrix (DBM) has been proposed as an alternative. We aim to identify the critical size defect of failure rates for ICBG and rhBMP-2/DBM. METHODS: A retrospective review evaluated patients undergoing ABG from 2016-2022. Patients with genetic syndromes, bilateral clefts, and missing postoperative cone beam computed tomography (CBCT) were excluded. The 3-dimensional volumetric defect sizes were calculated using preoperative CBCT scans. The primary outcome was bony bridge formation based on postoperative imaging. Logistic regression was used to model graft failure rates and identify the maximal point, which defined the critical point. RESULTS: Among 148 patients screened, 62 were included who underwent ABG (ICBG: n=28; rhBMP-2/DBM: n=34). There was no significant difference in bridge formation between graft types. The critical point in failure rate was calculated to be 829.3mm3 and 857.8mm3 for rhBMP-2/DBM and ICBG, respectively. Upon Fisher-exact analysis, there were increased bridge failures in clefts greater than the critical point for both ICBG (p<0.001) and rhBMP-2/DBM (p=0.005). The critical point did not vary between graft types (p=0.772) CONCLUSION: Our findings identified a higher probability of graft failure beyond the predicted critical size defect for each respective bone graft. Clinicians can better counsel families of patients with larger defects with a higher probability of treatment failure using either ICBG or rhBMP-2/DBM.

Spontaneous Osteogenic Potential of Periosteum after Segmental Mandibulectomy in Patients with Medication-Related Osteonecrosis of the Jaw (MRONJ): A Retrospective Study of 14 Cases

Medication-related osteonecrosis of the jaw (MRONJ) has chiefly involved patients receiving medications for the treatment of bone-related malignancies. The surgical methods are now cautiously recommended as the treatment option for MRONJ. The purpose of this retrospective study was to report new bone formation and examine possible factors influencing spontaneous bony bridge formation by using an R-plate for reconstruction without any graft material after segmental mandibulectomy in patients with MRONJ. A cohort of 54 patients who underwent mandibulectomy between 2017 and 2022 by a single operator were included. Of them, 14 MRONJ patients (12 females and 2 males) were selected based on the inclusion criteria. Data on new bone formation, bony bridge formation, R-plate fracture, patient age, and type and duration of medication were collected. The mean age of the patients was 74.8 ± 9.3 years. All patients showed new bone formation, and 71.4% showed bony bridge formation within a year after surgery. The older the patient, the lower was the tendency for bony bridge formation in the defect (p = 0.035). Statistical analysis was performed using Fisher’s exact test. Preservation of the periosteum might be one of the most important contributing factors to new bone formation, serving as an optimal treatment option for reconstruction after segmental mandibulectomy in patients with MRONJ.

Studying the Effect of Cross-Linking and Sulfonation on the Calcium-Binding Ability of Polystyrene Sulfonate in the Presence of Dodecyl Sulfate

Calcium ions in hard water deteriorate the cleaning performance of detergents by interacting with the anionic surfactants and inducing their precipitation. Polystyrene sulfonate is a common component of cation-exchange resins that adsorb hard ions such as Ca+2 and Mg+2, which adhere to the sulfonate groups. Therefore, understanding the calcium-binding ability of polystyrene sulfonate in the presence of dodecyl sulfate can help in designing novel water-softening agents for applications related to detergency. Studying the association between polystyrene sulfonate and dodecyl sulfate via calcium ion bridges is also important. Since resins contain cross-linked polystyrene sulfonate, degrees of cross-linking and sulfonation are two important parameters. We use molecular dynamics simulations to study the effect of the above parameters on the calcium-binding ability of isotactic polystyrene sulfonate in the presence of dodecyl sulfate. We observe negligible dependence of calcium-ion binding of polystyrene sulfonate on the degrees of cross-linking and sulfonation. The formation of calcium ion bridges between cross-linked polystyrene sulfonate and dodecyl sulfate is strongly affected by the degree of sulfonation. Such bridges are observed more for the intermediate degrees of sulfonation. This is because, at a very low degree of sulfonation, dodecyl sulfate ions align closer to the cross-linking aromatic groups than the sulfonated ones. On the other hand, at high degrees of sulfonation, stronger electrostatic repulsion disfavors the proximity between dodecyl sulfate and polystyrene sulfonate.

The Key Role of Chalcogenurane Intermediates in the Reduction Mechanism of Sulfoxides and Selenoxides by Thiols Explored In Silico.

Sulfoxides and selenoxides oxidize thiols to disulfides while being reduced back to sulfides and selenides. While the reduction mechanism of sulfoxides to sulfides has been thoroughly explored experimentally as well as computationally, less attention has been devoted to the heavier selenoxides. In this work, we explore the reductive mechanism of dimethyl selenoxide, as an archetypal selenoxide and, for the sake of comparison, the reductive mechanism of dimethyl sulfoxide to gain insight into the role of the chalcogen on the reaction substrate. Particular attention is devoted to the key role of sulfurane and selenurane intermediates. Moreover, the capacity of these system to oxidize selenols rather than thiols, leading to the formation of selenyl sulfide bridges, is explored in silico. Notably, this analysis provides molecular insight into the role of selenocysteine in methionine sulfoxide reductase selenoenzyme. The activation strain model of chemical reactivity is employed in the studied reactions as an intuitive tool to bridge the computationally predicted effect of the chalcogen on the chalcogenoxide as well as on the chalcogenol.

Enhanced fog collection of hydrogel-coated wires inspired by water film-trapping characteristics of Tillandsia

Fog collection has been widely studied to collect fresh water in arid regions. With the demand of optimizing the design of fog collectors, removing the pinned droplets and accelerating the water drainage have become a challenge. To address this challenge, we propose a fog collection method utilizing calcium alginate hydrogel-coated wires inspired by the water film-trapping characteristics of Tillandsia. Maintaining the effective wire diameter by water film trapped on the hydrogel, the fog collection performance of our hydrogel-coated wire precedes that of a bare wire in collection efficiency (up to 136 % higher) under different flow speed conditions. Significantly, retaining the inter-distance between dual-wires, the collection efficiency of hydrogel-coated dual-wires is 1.2 ∼ 1.7 times higher than that of two bare dual-wires. Moreover, the hydrogel-coated wires prevent the formation of water bridges between wires by removing the deposited droplets promptly, which opens different perspectives on designing the hydrogel-coated wires for the purpose of water harvesting, sustainable engineering, and ecofriendly technology.

Carbonate diagenesis: A celebration of the work of John Anthony Dawson (Tony) Dickson

Carbonate diagenesis: A celebration of the work of John Anthony Dawson (Tony) Dickson

Crystallographic and biophysical analysis of the fusion core from SARS‐CoV‐2 spike protein

AbstractSevere acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) is a newly emerging infectious pathogen causing coronavirus disease 2019 (COVID‐19). The virus primarily infects cells via its spike glycoprotein, which is cleaved into S1 and S2 subunits to aid in cell attachment and membrane fusion, respectively. Heptad repeat 1 (HR1) and heptad repeat 2 (HR2) of the S2 subunit are essential for membrane fusion, culminating in an expected six‐helix bundle termed fusion core. To better understand the structural and biophysical features of the SARS‐CoV‐2 fusion core, we designed, constructed, and bacterially produced a recombinant single‐chain HR1‐L6‐HR2 protein and conducted a series of biochemical and biophysical experiments. Our findings demonstrate that the HR1‐L6‐HR2 protein spontaneously assembles into a highly stable trimeric complex, further confirmed by x‐ray crystallographic analysis. The crystal structure of the fusion core reveals a trimeric coiled‐coil structure of HR1 antiparallelly surrounded by three HR2 to form a six‐helical bundle. Additionally, four residues of HR1 that contribute to binding with HR2 through the formation of hydrogen bonds and salt bridges were observed. These results indicate that the SARS‐CoV‐2 fusion core exhibits similar characteristics to other class I viral glycoproteins, suggesting potential for drug repurposing as an alternative strategy to combat COVID‐19.

TRAP1 S-nitrosylation as a model of population-shift mechanism to study the effects of nitric oxide on redox-sensitive oncoproteins

S-nitrosylation is a post-translational modification in which nitric oxide (NO) binds to the thiol group of cysteine, generating an S-nitrosothiol (SNO) adduct. S-nitrosylation has different physiological roles, and its alteration has also been linked to a growing list of pathologies, including cancer. SNO can affect the function and stability of different proteins, such as the mitochondrial chaperone TRAP1. Interestingly, the SNO site (C501) of TRAP1 is in the proximity of another cysteine (C527). This feature suggests that the S-nitrosylated C501 could engage in a disulfide bridge with C527 in TRAP1, resembling the well-known ability of S-nitrosylated cysteines to resolve in disulfide bridge with vicinal cysteines. We used enhanced sampling simulations and in-vitro biochemical assays to address the structural mechanisms induced by TRAP1 S-nitrosylation. We showed that the SNO site induces conformational changes in the proximal cysteine and favors conformations suitable for disulfide bridge formation. We explored 4172 known S-nitrosylated proteins using high-throughput structural analyses. Furthermore, we used a coarse-grained model for 44 protein targets to account for protein flexibility. This resulted in the identification of up to 1248 proximal cysteines, which could sense the redox state of the SNO site, opening new perspectives on the biological effects of redox switches. In addition, we devised two bioinformatic workflows (https://github.com/ELELAB/SNO_investigation_pipelines) to identify proximal or vicinal cysteines for a SNO site with accompanying structural annotations. Finally, we analyzed mutations in tumor suppressors or oncogenes in connection with the conformational switch induced by S-nitrosylation. We classified the variants as neutral, stabilizing, or destabilizing for the propensity to be S-nitrosylated and undergo the population-shift mechanism. The methods applied here provide a comprehensive toolkit for future high-throughput studies of new protein candidates, variant classification, and a rich data source for the research community in the NO field.

Long-term results comparison after anterior cervical discectomy with BGS-7 spacer (NOVOMAX®-C) and allograft spacer: A prospective observational study.

Introduction: In an anterior cervical discectomy and fusion (ACDF), various types of graft materials including autograft, allograft, and synthetic graft have been used to achieve adequate spinal fusion. Allograft spacer is mainly used in cervical fusion, especially in the anterior approach. The synthetic bone graft material BGS-7(CaO-SiO2-P2O5-B2O3, bioactive Glass-Ceramics) can bind with surrounding bone tissue by forming a hydroxyapatite layer bone bridge, leading to faster graft osseointegration. This study was conducted to compare long-term clinical outcome of BGS-7 spacer and allograft spacer for anterior cervical discectomy and fusion surgery. Materials and Methods: From September 2014 to December 2016, Consecutive anterior cervical discectomy and fusion surgeries using a BGS-7 spacer (N = 18) and Allograft spacer (N = 26) were compared for postoperative clinical outcomes. Radiologic assessments were performed, and Instrumental failure, including breakage, cage migration, subsidence were observed and Fusion status were analyzed. Finite element analysis was performed for simulating mechanical stress between the vertebral body and implant. Clinical outcomes were evaluated using neck VAS, NDI, and JOA on the patient's final follow-up visits. Results: Among the 44 patients who underwent an anterior cervical discectomy and fusion surgery using the BGS-7 spacer and Allograft spacer, there were 30 men and 14 women. The average age at the operation was 47.69 ± 10.49 in allograft spacer and 51.67 ± 11.03 in BGS-7 spacer. The mean follow-up period was 89.18 ± 5.44months. Twenty three (88.46%) patients in allograft spacer and 20(100%) patients in BGS-7 spacer were demonstrated radiologic evidence of interbody fusion in last OPD, which accounts for fusion grade 4 or 5. Peak stresses were 343.85MPa in allograft spacer, and 132.55MPa in BGS-7 spacer. Long-term clinical outcomes including neck VAS, NDI, and JOA didn't show statistical differences between the two groups. There were no adverse events related to the BGS-7 spacer.10.3389/fbioe.2023.110046. Conclusion: The BGS-7 spacer demonstrated reliability as a spacer in anterior cervical discectomy and fusionF surgery without instrumental failure. Early stabilization with a bony bridge formation was observed at the intermediate follow-up period, and the long-term clinical outcome was favorable at more than 60months after surgery without any adverse events. Thus, the BGS-7 spacer is a safe and effective alternative to the allograft spacer in anterior cervical discectomy and fusion surgery.

Multifunctional and biodegradable methacrylated gelatin/Aloe vera nanofibers for endodontic disinfection and immunomodulation

Currently employed approaches and materials used for vital pulp therapies (VPTs) and regenerative endodontic procedures (REPs) lack the efficacy to predictably achieve successful outcomes due to their inability to achieve adequate disinfection and/or lack of desired immune modulatory effects. Natural polymers and medicinal herbs are biocompatible, biodegradable, and present several therapeutic benefits and immune-modulatory properties; thus, standing out as a clinically viable approach capable of establishing a conducive environment devoid of bacteria and inflammation to support continued root development, dentinal bridge formation, and dental pulp tissue regeneration. However, the low stability and poor mechanical properties of the natural compounds have limited their application as potential biomaterials for endodontic procedures. In this study, Aloe vera (AV), as a natural antimicrobial and anti-inflammatory agent, was incorporated into photocrosslinkable Gelatin methacrylate (GelMA) nanofibers with the purpose of developing a highly biocompatible biomaterial capable of eradicating endodontic infection and modulating inflammation. Stable GelMA/AV nanofibers with optimal properties were obtained at the ratio of (70:30) by electrospinning. In addition to the pronounced antibacterial effect against Enterococcus faecalis, the GelMA/AV (70:30) nanofibers also exhibited a sustained antibacterial activity over 14 days and significant biofilm reduction with minimal cytotoxicity, as well as anti-inflammatory properties and immunomodulatory effects favoring healing. Our results indicate that the novel GelMA/AV (70:30) nanofibers hold great potential as a biomaterial strategy for endodontic infection eradication and enhanced healing.

New specimens and species of the Oligocene toothed baleen whaleCoronodonfrom South Carolina and the origin of Neoceti

Baleen whales (Mysticeti) are gigantic filter-feeding cetaceans possessing the unique soft tissue structure baleen and lacking adult teeth; Oligocene fossils have revealed a wealth of early diverging tooth-bearing mysticetes highlighting the transition from archaeocete ancestors to early toothless baleen-bearing eomysticetid whales. The archaeocete-like, toothed mysticeteCoronodon havensteinifrom the lower Oligocene Ashley Formation of South Carolina possesses a number of peculiar aspects of feeding morphology suggesting dental filter-feeding in the earliest diverging mysticete lineage. New fossils ofCoronodonare described in detail, including (1) supplementary description of the holotype skull and skeleton ofCoronodon havensteini; (2) description of two new juvenile skulls ofC. havensteiniand a partial skull and postcranial skeleton of an adult; (3) description of the new speciesCoronodon planifronsn.sp.; and (4) description of the new speciesCoronodon newtonorum. New specimens ofCoronodon havensteiniinclude a partial adult skeleton preserving new elements for the species including incisors, numerous upper premolars and molars, lower m4, scapula, lumbar, and caudal vertebrae, and two juvenile skulls with tympanoperiotics and teeth. Fossils from the overlying unit, the Chandler Bridge Formation, represent two new species:Coronodon newtonorumn. sp. andCoronodon planifronsn. sp.Coronodon newtonorumpossesses a concave-up alveolar profile, a mandibular condyle elevated far above the toothrow, and a gracile periotic resembling those of juvenileC. havensteini.Coronodon planifronsn. sp. possesses a horizontal supraorbital process, successively smaller upper molars, massively inflated periotic, and longer intertemporal region.Coronodon planifronsn. sp. preserves one of the most complete vertebral columns among toothed mysticetes, indicating nine thoracic vertebrae, ten lumbar vertebrae, and at least 20 caudal vertebrae. The column exhibits a somewhat stabilized caudal peduncle with enlarged lumbocaudal vertebrae, and rectangular terminal caudals indicate the presence of tail flukes. Juvenile skulls reveal several ontogenetic trends inCoronodon havensteini, including the anterior migration of the orbitotemporal crest, anteroposterior elongation of the intertemporal region, inflation of the body of the periotic, enlargement of the tympanic bulla, and continued postnatal emergence of the premolars and molars from their alveoli. Disarticulated skulls suggest a degree of rostral kinesis in this genus. Phylogenetic analysis of the largest assembled supermatrix of Mysticeti (n=138 OTUs; four archaeocetes, 10 odontocetes, 124 mysticetes; 391 morphological and 27,225 molecular characters) confirms placement ofCoronodonas the earliest diverging lineage of Mysticeti under equally weighted analyses whereas implied weighting placesCoronodonand similar taxa outside Neoceti, prompting a review of character transformations at the base of Neoceti.