In this review, we highlight the importance of nanostructure of cellulose-based biomaterials to allow cellular adhesion, the contribution of nanostructure to macroscale mechanical properties, and ...several key applications of these materials for fundamental scientific research and biomedical engineering. Different features on the nanoscale can have macroscale impacts on tissue function. Cellulose is a diverse material with tunable properties and is a promising platform for biomaterial development and tissue engineering. Cellulose-based biomaterials offer some important advantages over conventional synthetic materials. Here we provide an up-to-date summary of the status of the field of cellulose-based biomaterials in the context of bottom-up approaches for tissue engineering. We anticipate that cellulose-based material research will continue to expand because of the diversity and versatility of biochemical and biophysical characteristics highlighted in this review.
A variety of machine learning methods such as naive Bayesian, support vector machines and more recently deep neural networks are demonstrating their utility for drug discovery and development. These ...leverage the generally bigger datasets created from high-throughput screening data and allow prediction of bioactivities for targets and molecular properties with increased levels of accuracy. We have only just begun to exploit the potential of these techniques but they may already be fundamentally changing the research process for identifying new molecules and/or repurposing old drugs. The integrated application of such machine learning models for end-to-end (E2E) application is broadly relevant and has considerable implications for developing future therapies and their targeting.
► Pyrosequencing was applied to analyze compost prokaryotic communities. ► Communities were analyzed at each of the three major compost phases. ► In-depth census of community composition was attained ...and succession patterns revealed. ► Mesophilic- and mature-phase communities were distinct. ► This data on community composition may help determine biomarker assays for compost maturity.
In this study, 454-pyrosequencing was applied to analyze prokaryotic patterns in three lignocellulosic composting systems across the three main phases. In all composts, diversity expanded as composting progressed. Communities in the mesophilic- and mature-phases of all composts were distinct, which did not support the concept that organisms present in the mesophilic phase enter dormancy during thermophilic period, and re-colonize the compost at the mature phase. Analysis of similarity revealed compost phase was a significant source of dissimilarity (p=0.011), compost type was not (p=0.401). Analysis of variance also showed significant phase effects on the abundance of (p-value): Archaea (0.001), Planctomycetes (0.002), Chloroflexi (0.016), Deltaproteobacteria (0.027), Bacteria (0.046) and Gammaproteobacteria (0.056). Mature-phase compost was a preferred niche for the Archaea, Planctomycetes, Chloroflexi and Deltaproteobacteria, while Gammaproteobacteria were predominant in earlier phases. Thus, the mature phase pattern could have implications in the development of biomarker assays for compost maturity.
Hearts are the first organs to fail in animals exposed to heat stress. Predictions of climate change mediated increases in ocean temperatures suggest that the ectothermic heart may place tight ...constraints on the diversity and distribution of marine species with cardiovascular systems. For many such species, their upper temperature limits (Tmax) and respective heart failure (HF) temperature (T(HF)) are only a few degrees from current environmental temperatures. While the ectothermic cardiovascular system acts as an "ecological thermometer," the exact mechanism that mediates HF remains unresolved. We propose that heat-stressed cardiac mitochondria drive HF. Using a common New Zealand fish, Notolabrus celidotus, we determined the THF (27.5°C). Haemoglobin oxygen saturation appeared to be unaltered in the blood surrounding and within heat stressed hearts. Using high resolution respirometry coupled to fluorimeters, we explored temperature-mediated changes in respiration, ROS and ATP production, and overlaid these changes with T(HF). Even at saturating oxygen levels several mitochondrial components were compromised before T(HF). Importantly, the capacity to efficiently produce ATP in the heart is limited at 25°C, and this is prior to the acute T(HF) for N. celidotus. Membrane leakiness increased significantly at 25°C, as did cytochrome c release and permeability to NADH. Maximal flux rates and the capacity for the electron transport system to uncouple were also altered at 25°C. These data indicate that mitochondrial membrane integrity is lost, depressing ATP synthesis capacity and promoting cytochrome c release, prior to T(HF). Mitochondria can mediate HF in heat stressed hearts in fish and play a significant role in thermal stress tolerance, and perhaps limit species distributions by contributing to HF.
Gold nanoparticles (AuNPs) of various shapes (including spheres, stars and flowers), with similar dimensions, were synthesized and evaluated for their antibacterial effects toward
, a bacterium ...responsible for numerous life-threatening infections worldwide. Optical growth curve measurements and Gompertz modeling showed significant AuNP shape- and concentration-dependent decreases in bacterial growth with increases in bacterial growth lag time. To evaluate prospective use in in vivo systems, the cytotoxicity of the same AuNPs was evaluated toward human dermal fibroblasts in vitro by 3-(4,5 dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) viability assays and confocal microscopy. No indication of any mammalian cell toxicity or morphological effects was found. Additionally, it was observed that the AuNPs were readily internalized in fibroblasts after 4 days of incubation. Most importantly, the results of the present study showed that gold nanoflowers in particular possessed the most promising non-cytotoxic mammalian cell behavior with the greatest shape-dependent antibacterial activity-promising properties for their future investigation in a wide range of anti-infection applications.
Magnesium plays an important role in the body, mediating cell-extracellular matrix interactions and bone apatite structure and density. This study investigated, for the first time, the effects of ...adding magnesium oxide (MgO) nanoparticles to poly (l-lactic acid) (PLLA) and to hydroxyapatite (HA) nanoparticle-PLLA composites for orthopedic tissue engineering applications. Results showed that MgO nanoparticles significantly enhanced osteoblast adhesion and proliferation on HA-PLLA nanocomposites while maintaining mechanical properties (Young's modulus ∼1,000 MPa) suitable for cancellous bone applications. Additionally, osteoblasts (or bone-forming cells) cultured in the supernatant of degrading nanocomposites showed improved proliferation in the presence of magnesium, indicating that the increased alkalinity of solutions containing MgO nanocomposites had no toxic effects towards cells. These results together indicated the promise of further studying MgO nanoparticles as additive materials to polymers to enhance the integration of implanted biomaterials with bone.
Identification of new drug targets is vital for the advancement of drug discovery against Mycobacterium tuberculosis, especially given the increase of resistance worldwide to first- and second-line ...drugs. Because traditional target-based screening has largely proven unsuccessful for antibiotic discovery, we have developed a scalable platform for target identification in M. tuberculosis that is based on whole-cell screening, coupled with whole-genome sequencing of resistant mutants and recombineering to confirm. The method yields targets paired with whole-cell active compounds, which can serve as novel scaffolds for drug development, molecular tools for validation, and/or as ligands for co-crystallization. It may also reveal other information about mechanisms of action, such as activation or efflux. Using this method, we identified resistance-linked genes for eight compounds with anti-tubercular activity. Four of the genes have previously been shown to be essential: AspS, aspartyl-tRNA synthetase, Pks13, a polyketide synthase involved in mycolic acid biosynthesis, MmpL3, a membrane transporter, and EccB3, a component of the ESX-3 type VII secretion system. AspS and Pks13 represent novel targets in protein translation and cell-wall biosynthesis. Both MmpL3 and EccB3 are involved in membrane transport. Pks13, AspS, and EccB3 represent novel candidates not targeted by existing TB drugs, and the availability of whole-cell active inhibitors greatly increases their potential for drug discovery.
Cultured porcine cell lines are powerful tools for functional genomics and in vitro phenotypic testing of candidate causal variants. However, to be utilised for genomic or variant interrogation ...assays, the genome sequence and structure of cultured cell lines must be realised. In this work, we called variants and used read coverage in combination with within-sample allele frequency to detect potential aneuploidy in two immortalised porcine kidney epithelial (PK15) cell lines and in a pig embryonic fibroblast line.
We compared two PK15 cultured cells samples: a new American Type Culture Collection (ATCC) sample and one that has been utilised and passaged within the laboratory for an extended period (> 10 years). Read coverage and within-sample allele frequencies showed that several chromosomes are fully or partially aneuploid in both PK15 lines, including potential trisomy of chromosome 4 and tetrasomy of chromosome 17. The older PK15 line showed evidence of additional structural variation and potentially clonal variation. By comparison, the pig embryonic fibroblast line was free from the gross aneuploidies seen in the PK15s.
Our results show that the PK15 cell lines examined have aneuploidies and complex structural variants in their genomes. We propose that screening for aneuploidy should be considered for cell lines, and discuss implications for livestock genomics.
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