Aims
Otitis externa (OE), one of the most common ear diseases in dogs, is caused by bacterial pathogens such as Staphylococcus sp. To understand the network of microbial communities in the canine ear ...canal affected with OE, we performed a cross‐sectional study using next‐generation sequencing.
Methods and Results
Ear swab samples were collected from 23 OE‐affected and 10 healthy control dogs, and the 16S rRNA gene sequenced using Illumina MiSeq. The otic microbiota in the OE‐affected dogs showed significantly decreased alpha diversity compared to controls. The community composition also differed in the affected group, with significantly higher relative abundance of the phylum Firmicutes and the genus Staphylococcus (P = 0·01 and 0·04 respectively). Contrary to our expectations, the severity of the disease did not impact the otic microbiota in OE‐affected dogs.
Conclusions
The ear canal microbiota of OE‐affected dogs is distinct from that of healthy dogs, irrespective of disease status.
Significance and Impact of the Study
This study, one of the few detailed analyses of the otic microbiota, can provide practical information for the appropriate treatment of canine OE.
To use solar irradiation or interior lighting efficiently, we sought a photocatalyst with high reactivity under visible light. Films and powders of TiO2-xNxhave revealed an improvement over titanium ...dioxide (TiO2) under visible light (wavelength < 500 nanometers) in optical absorption and photocatalytic activity such as photodegradations of methylene blue and gaseous acetaldehyde and hydrophilicity of the film surface. Nitrogen doped into substitutional sites of TiO2has proven to be indispensable for band-gap narrowing and photocatalytic activity, as assessed by first-principles calculations and x-ray photoemission spectroscopy.
Gene co-expression, in many cases, implies the presence of a functional linkage between genes. Co-expression analysis has uncovered gene regulatory mechanisms in model organisms such as Escherichia ...coli and yeast. Recently, accumulation of Arabidopsis microarray data has facilitated a genome-wide inspection of gene co-expression profiles in this model plant. An approach using network analysis has provided an intuitive way to represent complex co-expression patterns between many genes. Co-expression network analysis has enabled us to extract modules, or groups of tightly co-expressed genes, associated with biological processes. Furthermore, integrated analysis of gene expression and metabolite accumulation has allowed us to hypothesize the functions of genes associated with specific metabolic processes. Co-expression network analysis is a powerful approach for data-driven hypothesis construction and gene prioritization, and provides novel insights into the system-level understanding of plant cellular processes.
In polymerisation, organic peroxides are widely used as polymerisation initiators, which are indispensable in the production of general purpose resins such as the low-density polyethylene used for ...plastic bags and various types of film, the PVC used for pipes and gutters, and the acrylic resins used in various types of paint. After 2 minutes 75% has decomposed, after 3 minutes 87.5% has decomposed, and calculation shows that after 6-8 minutes almost the entire amount will have decomposed. ...a heating time of 6-8 minutes is required for thermal processing at the 1-minute half-life temperature. ...if, on adding more organic peroxide in order to increase grafting, the number of radicals on the main chain increases, crosslinking will be promoted simultaneously. Highly crosslinked maleic anhydride-modified PE is less compatible in matrix PE, and so the strength is decreased due to incompatibility; it also has lower surface reactivity with the filler, and therefore has a negative effect with regard to improving the physical properties of the compound.
Purpose To quantify the reported failures and reoperations for the emerging technique of matrix-assisted cartilage repair at short-term and midterm follow-up. Methods We conducted a systematic review ...of 3 databases from March 2004 to February 2014 using keywords important for articular cartilage repair. Two authors reviewed the articles, the study exclusion criteria were applied, and articles were determined to be relevant (or not) to the research question. All studies with a minimum of 2 years' clinical follow-up were reviewed for all reported reoperations. The reasons for reoperations were recorded. Results We reviewed 66 articles from the 301 articles identified in the original systematic search. There were 60 articles on matrix-assisted cartilage transplantation and 6 articles on matrix-induced chondrogenesis. The matrix-assisted cartilage transplantation studies reported on a total of 1,380 patients at 2 to 5 years' follow-up. Among these, there were 72 reoperations (5%) including 46 treatment failures (3%). These numbers increased to an 11% reoperation rate and 9% treatment failure rate at minimum 5-year follow-up of 961 patients. The most common procedures performed other than revision cartilage surgery or arthroplasty were manipulation under anesthesia for arthrofibrosis (0.7%) and debridement for graft hypertrophy (1.2%). The matrix-induced chondrogenesis studies reported on 163 patients. Among these, there were 15 reoperations (9%) that included 4 treatment failures (2%), 9 manipulations under anesthesia (6%), and 2 debridements for graft hypertrophy (1%). Conclusions Treatment failure rates for matrix-assisted cartilage repair increase from short-term to midterm follow-up, with 11% of patients having undergone further surgery at a minimum of 5 years' follow-up. These data can be used to counsel patients on the potential need for further operative intervention after this emerging cartilage repair technique. Level of Evidence Level IV, systematic review of Level I through IV studies.
The seven serotypes (A–G) of botulinum neurotoxin (BoNT) are proteins produced by Clostridium botulinum and have multifunctional abilities: (i) they target cholinergic nerve endings via binding to ...ecto‐acceptors (ii) they undergo endocytosis/translocation and (iii) their light chains act intraneuronally to block acetylcholine release. The fundamental process of quantal transmitter release occurs by Ca2+‐regulated exocytosis involving sensitive factor attachment protein‐25 (SNAP‐25), syntaxin and synaptobrevin. Proteolytic cleavage by BoNT‐A of nine amino acids from the C‐terminal of SNAP‐25 disables its function, causing prolonged muscle weakness. This unique combination of activities underlies the effectiveness of BoNT‐A haemagglutinin complex in treating human conditions resulting from hyperactivity at peripheral cholinergic nerve endings. In vivo imaging and immunomicroscopy of murine muscles injected with type A toxin revealed that the extended duration of action results from the longevity of its protease, persistence of the cleaved SNAP‐25 and a protracted time course for the remodelling of treated nerve–muscle synapses. In addition, an application in pain management has been indicated by the ability of BoNT to inhibit neuropeptide release from nociceptors, thereby blocking central and peripheral pain sensitization processes. The widespread cellular distribution of SNAP‐25 and the diversity of the toxin's neuronal acceptors are being exploited for other therapeutic applications.
Homeostasis is a recurring theme in biology that ensures that regulated variables robustly-and in some systems, completely-adapt to environmental perturbations. This robust perfect adaptation feature ...is achieved in natural circuits by using integral control, a negative feedback strategy that performs mathematical integration to achieve structurally robust regulation
. Despite its benefits, the synthetic realization of integral feedback in living cells has remained elusive owing to the complexity of the required biological computations. Here we prove mathematically that there is a single fundamental biomolecular controller topology
that realizes integral feedback and achieves robust perfect adaptation in arbitrary intracellular networks with noisy dynamics. This adaptation property is guaranteed both for the population-average and for the time-average of single cells. On the basis of this concept, we genetically engineer a synthetic integral feedback controller in living cells
and demonstrate its tunability and adaptation properties. A growth-rate control application in Escherichia coli shows the intrinsic capacity of our integral controller to deliver robustness and highlights its potential use as a versatile controller for regulation of biological variables in uncertain networks. Our results provide conceptual and practical tools in the area of cybergenetics
, for engineering synthetic controllers that steer the dynamics of living systems
.
Bacterial contact-dependent growth inhibition (CDI) is mediated by the CdiA/CdiB family of two-partner secretion proteins. Each CdiA protein exhibits a distinct growth inhibition activity, which ...resides in the polymorphic C-terminal region (CdiA-CT). CDI(+) cells also express unique CdiI immunity proteins that specifically block the activity of cognate CdiA-CT, thereby protecting the cell from autoinhibition. Here we show that many CDI systems contain multiple cdiA gene fragments that encode CdiA-CT sequences. These "orphan" cdiA-CT genes are almost always associated with downstream cdiI genes to form cdiA-CT/cdiI modules. Comparative genome analyses suggest that cdiA-CT/cdiI modules are mobile and exchanged between the CDI systems of different bacteria. In many instances, orphan cdiA-CT/cdiI modules are fused to full-length cdiA genes in other bacterial species. Examination of cdiA-CT/cdiI modules from Escherichia coli EC93, E. coli EC869, and Dickeya dadantii 3937 confirmed that these genes encode functional toxin/immunity pairs. Moreover, the orphan module from EC93 was functional in cell-mediated CDI when fused to the N-terminal portion of the EC93 CdiA protein. Bioinformatic analyses revealed that the genetic organization of CDI systems shares features with rhs (rearrangement hotspot) loci. Rhs proteins also contain polymorphic C-terminal regions (Rhs-CTs), some of which share significant sequence identity with CdiA-CTs. All rhs genes are followed by small ORFs representing possible rhsI immunity genes, and several Rhs systems encode orphan rhs-CT/rhsI modules. Analysis of rhs-CT/rhsI modules from D. dadantii 3937 demonstrated that Rhs-CTs have growth inhibitory activity, which is specifically blocked by cognate RhsI immunity proteins. Together, these results suggest that Rhs plays a role in intercellular competition and that orphan gene modules expand the diversity of toxic activities deployed by both CDI and Rhs systems.
Botulinum neurotoxin serotype A (BoNT/A) causes transient muscle paralysis by entering motor nerve terminals (MNTs) where it cleaves the SNARE protein Synaptosomal-associated protein 25 (SNAP25206) ...to yield SNAP25197. Cleavage of SNAP25 results in blockage of synaptic vesicle fusion and inhibition of the release of acetylcholine. The specific uptake of BoNT/A into pre-synaptic nerve terminals is a tightly controlled multistep process, involving a combination of high and low affinity receptors. Interestingly, the C-terminal binding domain region of BoNT/A, HC/A, is homologous to fibroblast growth factors (FGFs), making it a possible ligand for Fibroblast Growth Factor Receptors (FGFRs). Here we present data supporting the identification of Fibroblast Growth Factor Receptor 3 (FGFR3) as a high affinity receptor for BoNT/A in neuronal cells. HC/A binds with high affinity to the two extra-cellular loops of FGFR3 and acts similar to an agonist ligand for FGFR3, resulting in phosphorylation of the receptor. Native ligands for FGFR3; FGF1, FGF2, and FGF9 compete for binding to FGFR3 and block BoNT/A cellular uptake. These findings show that FGFR3 plays a pivotal role in the specific uptake of BoNT/A across the cell membrane being part of a larger receptor complex involving ganglioside- and protein-protein interactions.
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