Hydecleveland6673

he preclinical data and clinical trial results proved the feasibility, safety, and efficacy of the investigated material for jaw bone grafting, allowing us to bring the world's first gene-activated bone substitute from bench to bedside.The Achilles tendon (AT) has complex function in walking, exchanging energy due to loading by the triceps surae muscles. AT structure comprises three subtendons which exhibit variable twist among themselves and between individuals. Our goal was to create 3D finite element (FE) models to explore AT structure-function relationships. By simulating subtendon loading in FE models with different twisted geometries, we investigated how anatomical variation in twisted tendon geometry impacts fascicle lengths, strains, and energy storage. Three tendon FE models, built with elliptical cross sections based on average cadaver measurements, were divided into subtendons with varied geometric twist (low, medium, and high) and equal proportions. Tendon was modeled as transversely isotropic with fascicle directions defined using Laplacian flow simulations, producing fascicle twist. Prescribed forces, representing AT loading during walking, were applied to proximal subtendon ends, with distal ends fixed, and tuned to produce equal tendon elongation in each case, consistent with ultrasound measurements. Subtendon fascicle lengths were greater than free tendon lengths in all models by 1-3.2 mm, and were longer with greater subtendon twist with differences of 1.2-1.9 mm from low to high twist. Subtendon along-fiber strains were lower with greater twist with differences of 1.4-2.6%, and all were less than free tendon longitudinal strain by 2-5.5%. Energy stored in the AT was also lower with greater twist with differences of 1.8-2.4 J. With greater subtendon twist, similar elongation of the AT results in lower tissue strains and forces, so that longitudinal stiffness of the AT is effectively decreased, demonstrating how tendon structure influences mechanical behavior.Terpenes constitute the largest class of secondary metabolites in plants. Some terpenes are essential for plant growth and development, membrane components, and photosynthesis. Terpenes are also economically useful for industry, agriculture, and pharmaceuticals. However, there is very low content of most terpenes in microbes and plants. Chemical or microbial synthesis of terpenes are often costly. Plants have the elaborate and economic biosynthetic way of producing high-value terpenes through photosynthesis. Here we engineered the heterogenous sesquiterpenoid patchoulol production in A. annua. When using a strong promoter such as 35S to over express the avian farnesyl diphosphate synthase gene and patchoulol synthase gene, the highest content of patchoulol was 52.58 μg/g DW in transgenic plants. When altering the subcellular location of the introduced sesquiterpene synthetase via a signal peptide, the accumulation of patchoulol was observably increased to 273 μg/g DW. This case demonstrates that A. annua plant with glandular trichomes is a useful platform for synthetic biology studies.Protein kinase B (AKT1) is hyper-activated in diverse human tumors. AKT1 is activated by phosphorylation at two key regulatory sites, Thr308 and Ser473. Active AKT1 phosphorylates many, perhaps hundreds, of downstream cellular targets in the cytosol and nucleus. AKT1 is well-known for phosphorylating proteins that regulate cell survival and apoptosis, however, the full catalog of AKT1 substrates remains unknown. Using peptide arrays, we recently discovered that each phosphorylated form of AKT1 (pAKT1S473, pAKT1T308, and ppAKT1S473,T308) has a distinct substrate specificity, and these data were used to predict potential new AKT1 substrates. To test the high-confidence predictions, we synthesized target peptides representing putative AKT1 substrates. Peptides substrates were synthesized by solid phase synthesis and their purity was confirmed by mass spectrometry. Most of the predicted peptides showed phosphate accepting activity similar to or greater than that observed with a peptide derived from a well-established AKT1 substrate, glycogen synthase kinase 3β (GSK-3β). Among the novel substrates, AKT1 was most active with peptides representing PIP3-binding protein Rab11 family-interacting protein 2 and cysteinyl leukotriene receptor 1, indicating their potential role in AKT1-dependent cellular signaling. The ppAKT1S473,T308 enzyme was highly selective for peptides containing a patch of basic residues at -5, -4, -3 and aromatic residues (Phe/Tyr) at +1 positions from the phosphorylation site. The pAKT1S473 variant preferred more acidic peptides, Ser or Pro at +4, and was agnostic to the residue at -5. The data further support our hypothesis that Ser473 phosphorylation plays a key role in modulating AKT1 substrate selectivity.Polyhydroxyalkanoates (PHAs) are naturally occurring biopolymers produced by microorganisms. PHAs have become attractive research biomaterials in the past few decades owing to their extensive potential industrial applications, especially as sustainable alternatives to the fossil fuel feedstock-derived products such as plastics. Among the biopolymers are the bioplastics and oligomers produced from the fermentation of renewable plant biomass. Bioplastics are intracellularly accumulated by microorganisms as carbon and energy reserves. The bioplastics, however, can also be produced through a biochemistry process that combines fermentative secretory production of monomers and/or oligomers and chemical synthesis to generate a repertoire of biopolymers. PHAs are particularly biodegradable and biocompatible, making them a part of today's commercial polymer industry. Their physicochemical properties that are similar to those of petrochemical-based plastics render them potential renewable plastic replacements. The design of efficient tractable processes using renewable biomass holds key to enhance their usage and adoption. In 2008, a lactate-polymerizing enzyme was developed to create new category of polyester, lactic acid (LA)-based polymer and related polymers. This review aims to introduce different strategies including metabolic and enzyme engineering to produce LA-based biopolymers and related oligomers that can act as precursors for catalytic synthesis of polylactic acid. As the cost of PHA production is prohibitive, the review emphasizes attempts to use the inexpensive plant biomass as substrates for LA-based polymer and oligomer production. Future prospects and challenges in LA-based polymer and oligomer production are also highlighted.PAL (phenylalanine ammonia lyase) is important for secondary metabolite production in plants and microorganisms. There is broad interest in engineering PAL for its biocatalytic applications in industry, agriculture, and medicine. The production of quantities of high-activity enzymes has been explored by gene cloning and heterogeneous expression of the corresponding protein. Here, we cloned the cDNA of Rhodotorula glutinis PAL (RgPAL) and introduced codon optimization to improve protein expression in Escherichia coli and enzyme activities in vitro. The RgPAL gene was cloned by reverse transcription and named pal-wt. It had a full-length of 2,121 bp and encoded a 706-amino-acid protein. The pal-wt was inefficiently expressed in E. coli, even when the expression host and physical conditions were optimized. Therefore, codon optimization was used to obtain the corresponding gene sequence, named pal-opt, in order to encode the same amino acid for the RgPAL protein. The recombinant protein encoded by pal-opt, named PAL-opt, was successfully expressed in E. coli and then purified to detect its enzymatic activity in vitro. Consequently, 55.33 ± 0.88 mg/L of PAL-opt protein with a specific activity of 1,219 ± 147 U/mg and Km value of 609 μM for substrate L-phenylalanine was easily obtained. The enzyme protein also displayed tyrosine ammonia lyase (TAL)-specific activity of 80 ± 2 U/mg and Km value of 13.3 μM for substrate L-tyrosine. The bifunctional enzyme RgPAL/TAL (PAL-opt) and its easy expression advantage will provide an important basis for further applications.Background The purpose of this study was to evaluate the risk of peri-prosthetic fracture of constructs made with cephalomedullary (CM) long and short nails. The nails were made with titanium alloy (Ti-6Al-4V) and stainless steel (SS 316L). Methods Biomechanical evaluation of CM nail constructs was carried out with regard to post-primary healing to determine the risk of peri-implant/peri-prosthetic fractures. PFK15 Therefore, this research comprised of, non-fractured, twenty-eight pairs of cadaveric femora that were randomized and implanted with four types of fixation CM nails resulting in four groups. These constructs were cyclically tested in bi-axial mode for up to 30,000 cycles. All the samples were then loaded to failure to measure failure loads. Three frameworks were carried out through this investigation, Michaelis-Menten, phenomenological, and probabilistic Monte Carlo simulation to model and predict damage accumulation. Findings Damage accumulation resulting from bi-axial cyclic loading in terms of construct stiffness was represented by Michaelis-Menten equation, and the statistical analysis demonstrated that one model can explain the damage accumulation during cyclic load for all four groups of constructs (P > 0.05). A two-stage stiffness drop was observed. The short stainless steel had a significantly higher average damage (0.94) than the short titanium nails (0.90, P 0.05). Results showed gender had a significant effect on load to failure in both torsional and bending tests (P less then 0.05 and P less then 0.001, respectively). Interpretation Kaplan-Meier survival analysis supports the use of short titanium CM nail. We recommend that clinical decisions should take age and gender into consideration in the selection of implants.Agricultural wastes, such as rice straw (RS) and pig manure (PM), cause serious environmental pollution due to the non-existence of effective disposal methods. Urgent investigations are needed to explore how such wastes can be transformed into resources. In this study, we comprehensively assessed methane yield and kinetics of RS and PM anaerobic co-digestion, with or without pretreatment of a previously developed cellulolytic microflora, under conditions of their maximum organic loading rate. The anaerobic co-digestion results revealed that the cumulative methane production of RS and PM after bio-pretreatment was 342.35 ml (g-VS)-1, which is 45% higher than that of the control group [236.03 ml·(g-VS)-1]. Moreover, the kinetic analysis showed the first-order kinetic, while the modified Gompertz models revealed higher fitting properties (R2 ≥ 0.966). After bio-pretreatment, the hydrolytic constant, maximum accumulative methane production, and maximum methane production rates of RS and PM reached 0.46 day-1, 350.79 ml·(g-VS)-1, and 45.36 ml·(g-VS)-1·day-1, respectively, which were 77, 45.1, and 84.3% higher than those without pretreatment. Also, we found that the lag phase and effective methane production time after bio-pretreatment decreased from 2.43 to 1.79 days and 10.7 to 8.92 days, respectively. Upon energy balance evaluation, we reported a net energy output of 5133.02 kWh·ton-1 after bio-pretreatment. Findings from this present study demonstrated that bio-pretreatment of RS and PM mixtures with cellulolytic microflora could greatly enhance methane production and anaerobic digestion efficiency.