- Controlling nitritation in a continuous split-feed/aeration biofilm nitrifying bioreactor. [Journal Article]
- BTBioresour Technol 2019 Jun 04; 288:121599
- This study explored the stability of partial ammonium oxidation at low feed concentration (50 g N/m3), suitable for anammox process, in continuous fixed bed up-flow biofilm reactors with external rec…
This study explored the stability of partial ammonium oxidation at low feed concentration (50 g N/m3), suitable for anammox process, in continuous fixed bed up-flow biofilm reactors with external recirculation-aeration. The reactors, filled with crushed basalt, were fed with synthetic medium at 20-25 °C at constant flow-rate with limiting dissolved oxygen concentration controlled by the recirculation ratio (R). Successful nitritation was achieved at R ≅ 4-6 with approx. 50% of NH4+ oxidized to NO2- with <5% NO3-accumulation. q-PCR analysis along the reactor showed ammonia oxidizing bacteria being the prevalent nitrifiers over the three-fourths of the bed in the flow direction, negligible denitrifiers and absent ammonium oxidizing archaea. A numerical model for predicting the concentration of the nitrogen species and DO was formulated. The model successfully predicted the experimental results and displayed good sensitivity to intrinsic oxygen uptake parameters. The proposed numerical model can serve both as an operational and design tool.
- Anti-repulsive guidance molecule-a antibody treatment and repetitive transcranial magnetic stimulation have synergistic effects on motor recovery after spinal cord injury. [Journal Article]
- NLNeurosci Lett 2019 Jun 11; :134329
- Damaged axons in the adult central nervous system (CNS) fail to regenerate spontaneously due to several intrinsic and extrinsic factors that inhibit axon elongation. An extrinsic inhibitory factor, r…
Damaged axons in the adult central nervous system (CNS) fail to regenerate spontaneously due to several intrinsic and extrinsic factors that inhibit axon elongation. An extrinsic inhibitory factor, repulsive guidance molecule-a (RGMa), is upregulated around spinal cord lesion sites. Inhibition of RGMa using an antibody promotes axon sprouting, regeneration, and motor recovery after spinal cord injury (SCI) in rodents and primates. Repetitive transcranial magnetic stimulation (rTMS) has been used as a form of rehabilitation, and accumulating studies have suggested that rTMS is able to modulate neural plasticity of the cortex. Here, we conducted rTMS with anti-RGMa antibody treatment in mice with SCI to investigate the potential synergistic effects on motor recovery. Although mice treated with anti-RGMa antibody and rTMS concomitantly did not show significant motor recovery, mice treated sequentially with anti-RGMa antibody followed by rTMS showed better motor performance than mice treated with anti-RGMa antibody alone. Moreover, we found that Ca2+/calmodulin-dependent kinase II (CaMKII) was upregulated in mice treated with anti-RGMa antibody and rTMS sequentially compared with mice received a single anti-RGMa antibody treatment. These results suggest that anti-RGMa antibody treatment and rTMS intervention have synergistic effects on motor recovery, and that the timing of rTMS intervention is a critical factor to maximize the effect of anti-RGMa antibody treatment. These interventions may provide new therapeutic strategies for promoting motor recovery after SCI.
- Hypercholesterolemia affects cardiac function, infarct size and inflammation in APOE*3-Leiden mice following myocardial ischemia-reperfusion injury. [Journal Article]
- PlosPLoS One 2019; 14(6):e0217582
- CONCLUSIONS: Diet-induced hypercholesterolemia caused impaired LV function eight weeks after MI-R injury despite a reduced post-ischemic infarct size. This was preceded by a pre-ischemic peripheral monocytosis, while there was a suppressed accumulation of inflammatory cells in the ischemic-reperfused myocardium after eight weeks. This experimental model using hypercholesterolemic APOE*3-Leiden mice exposed to MI-R seems suitable to study novel cardioprotective therapies in a more clinically relevant animal model.
- Pathogenicity and functional impact of non-frameshifting insertion/deletion variation in the human genome. [Journal Article]
- PCPLoS Comput Biol 2019 Jun 14; 15(6):e1007112
- Differentiation between phenotypically neutral and disease-causing genetic variation remains an open and relevant problem. Among different types of variation, non-frameshifting insertions and deletio…
Differentiation between phenotypically neutral and disease-causing genetic variation remains an open and relevant problem. Among different types of variation, non-frameshifting insertions and deletions (indels) represent an understudied group with widespread phenotypic consequences. To address this challenge, we present a machine learning method, MutPred-Indel, that predicts pathogenicity and identifies types of functional residues impacted by non-frameshifting insertion/deletion variation. The model shows good predictive performance as well as the ability to identify impacted structural and functional residues including secondary structure, intrinsic disorder, metal and macromolecular binding, post-translational modifications, allosteric sites, and catalytic residues. We identify structural and functional mechanisms impacted preferentially by germline variation from the Human Gene Mutation Database, recurrent somatic variation from COSMIC in the context of different cancers, as well as de novo variants from families with autism spectrum disorder. Further, the distributions of pathogenicity prediction scores generated by MutPred-Indel are shown to differentiate highly recurrent from non-recurrent somatic variation. Collectively, we present a framework to facilitate the interrogation of both pathogenicity and the functional effects of non-frameshifting insertion/deletion variants. The MutPred-Indel webserver is available at http://mutpred.mutdb.org/.
- Cytosine-5 RNA methylation links protein synthesis to cell metabolism. [Journal Article]
- PBPLoS Biol 2019 Jun 14; 17(6):e3000297
- Posttranscriptional modifications in transfer RNA (tRNA) are often critical for normal development because they adapt protein synthesis rates to a dynamically changing microenvironment. However, the …
Posttranscriptional modifications in transfer RNA (tRNA) are often critical for normal development because they adapt protein synthesis rates to a dynamically changing microenvironment. However, the precise cellular mechanisms linking the extrinsic stimulus to the intrinsic RNA modification pathways remain largely unclear. Here, we identified the cytosine-5 RNA methyltransferase NSUN2 as a sensor for external stress stimuli. Exposure to oxidative stress efficiently repressed NSUN2, causing a reduction of methylation at specific tRNA sites. Using metabolic profiling, we showed that loss of tRNA methylation captured cells in a distinct catabolic state. Mechanistically, loss of NSUN2 altered the biogenesis of tRNA-derived noncoding fragments (tRFs) in response to stress, leading to impaired regulation of protein synthesis. The intracellular accumulation of a specific subset of tRFs correlated with the dynamic repression of global protein synthesis. Finally, NSUN2-driven RNA methylation was functionally required to adapt cell cycle progression to the early stress response. In summary, we revealed that changes in tRNA methylation profiles were sufficient to specify cellular metabolic states and efficiently adapt protein synthesis rates to cell stress.
- Quasi-Atomic Bond Analyses in the Sixth Period: I. Relativistic Accurate Atomic Minimal Basis Sets for the Elements Cesium to Radon. [Journal Article]
- JPJ Phys Chem A 2019 Jun 14
- Full-valence relativistic accurate atomic minimal basis set (AAMBS) orbitals are developed for the sixth-row elements from cesium to radon, including the lanthanides. Saturated primitive atomic basis…
Full-valence relativistic accurate atomic minimal basis set (AAMBS) orbitals are developed for the sixth-row elements from cesium to radon, including the lanthanides. Saturated primitive atomic basis sets are developed and subsequently used to form the AAMBS orbitals. By virtue of the use of a saturated basis, properties computed based on the AAMBS orbitals are basis set independent. In molecules, the AAMBS orbitals can be used to construct valence virtual orbitals (VVOs) that provide chemically meaningful ab initio lowest unoccupied molecular orbitals (LUMOs) with basis set independent orbital energies. The optimized occupied molecular orbitals complemented with the VVOs form a set of full-valence molecular orbitals. They can be transformed into a set of oriented quasi-atomic orbitals (QUAOs) that provide information on intramolecular bonding via an intrinsic density analysis. In the present work, the development of the AAMBS for the sixth row is presented.
- Polydopamine-Based Interfacial Engineering of Extracellular Matrix Hydrogels for Construction and Long-Term Maintenance of Living Three-Dimensional Tissues. [Journal Article]
- AAACS Appl Mater Interfaces 2019 Jun 14
- Diverse biological processes in the body rely on the ability of cells to exert contractile forces on their extracellular matrix (ECM). In three-dimensional (3D) cell culture, however, this intrinsic …
Diverse biological processes in the body rely on the ability of cells to exert contractile forces on their extracellular matrix (ECM). In three-dimensional (3D) cell culture, however, this intrinsic cellular property can cause unregulated contraction of ECM hydrogel scaffolds, leading to a loss of surface anchorage and the resultant structural failure of in vitro tissue constructs. Despite advances in 3D culture technology, this issue remains a significant challenge in the development and long-term maintenance of physiological 3D in vitro models. Here we present a simple yet highly effective and accessible solution to this problem. We leveraged a single-step surface functionalization technique based on polydopamine to drastically increase the strength of adhesion between hydrogel scaffolds and cell culture substrates. Our method is compatible with different types of ECM and polymeric surfaces, and also permits prolonged shelf storage of functionalized culture substrates. The proof-of-principle of this technique was demonstrated by stable long-term (one month) 3D culture of human lung fibroblasts. Furthermore, we showed the robustness and advanced application of the method by constructing a dynamic cell stretching system and performing over 100,000 cycles of mechanical loading on 3D multicellular constructs for visualization and quantitative analysis of stretch-induced tissue alignment. Finally, we demonstrated the potential of our technique for the development of microphysiological in vitro models by establishing microfluidic 3D co-culture of vascular endothelial cells and fibroblasts to engineer self-assembled, perfusable 3D microvascular beds.
- Enhancing the magneto-optical effects in low-biased gyromagnetic media via photonic doping. [Journal Article]
- OLOpt Lett 2019 Jun 15; 44(12):3050-3053
- Enhancing nonreciprocal light-matter interaction at subwavelength scales has attracted enormous attention due to high demand for compact optical isolators. Here, we propose a significant enhancement …
Enhancing nonreciprocal light-matter interaction at subwavelength scales has attracted enormous attention due to high demand for compact optical isolators. Here, we propose a significant enhancement of the magneto-optical effect in low-biased gyromagnetic media via photonic doping. Magnetic particles immersed in a gyrotropy-near-zero medium act as dopants that largely modify the macroscopic gyromagnetic effects as well as the gyroelectric ones. Around the resonance frequency, the gyromagnetic activity is largely increased and even exceeds unity, thus providing a photonic band in which the wavenumber of one circularly polarized wave becomes purely imaginary. The sign of gyromagnetic activity flips at two chiral modes, and an equivalent switching of the external bias is revealed. A proof-of-concept low-biased planar isolator is designed with a thickness of only 1/28 wavelength and a degree of isolation achieving as high as 0.94. This methodology is robust against disturbance of the biased magnetic field and can be flexibly extended to other frequencies, thus offering a promising platform to achieve giant optical isolation with infinitesimally intrinsic magneto-optical effects and reduced sizes.
- Coding strategies in the otolith system differ for translational head motion vs static orientation relative to gravity. [Journal Article]
- EElife 2019 Jun 14; 8
- The detection of gravito-inertial forces by the otolith system is essential for our sense of balance and accurate perception. To date, however, how this system encodes self-motion stimuli experienced…
The detection of gravito-inertial forces by the otolith system is essential for our sense of balance and accurate perception. To date, however, how this system encodes self-motion stimuli experienced during everyday activities remains unknown. Here we directly addressed this fundamental question by recording from single otolith afferents in monkeys during naturalistic translational self-motion and changes in static head orientation. Otolith afferents with higher intrinsic variability transmitted overall more information about translational self-motion than their regular counterparts, due to stronger nonlinearities that enabled precise spike timing including phase locking. In contrast, more regular afferents better discriminated between different static head orientations relative to gravity. Using computational methods, we further demonstrated that coupled increases in intrinsic variability and sensitivity accounted for observed functional differences between afferent classes. Together, our results indicate that irregular and regular otolith afferents may use different strategies to encode naturalistic self-motion and static head orientation relative to gravity.
New Search Next
- NIR-Responsive Polypeptide Nanocomposite Generates NO Gas, Mild Photothermia and Chemotherapy to Reverse Multidrug Resistant Cancer. [Journal Article]
- NLNano Lett 2019 Jun 14
- Multidrug resistance (MDR) of cancers that results from overexpression of P-glycoprotein (P-gp) transporter mainly causes chemotherapy (CT) failure and hinders clinical transitions of current polypep…
Multidrug resistance (MDR) of cancers that results from overexpression of P-glycoprotein (P-gp) transporter mainly causes chemotherapy (CT) failure and hinders clinical transitions of current polypeptide nanomedicines. Herein, a novel polypeptide nanocomposite PNOC-PDA that integrates heat-sensitive NO gas delivery and photothermal conversion attributes can overcome MDR and maximize CT; meanwhile the optimized CT and intracellular high-concentration NO gas can assist a mild photothermal therapy (PTT) to eradicate cancer cells. The triple therapies produced superior and synergistic effect on MDR-reversal and killing MCF-7/ADR in vitro, and the P-gp expression level was downregulated to 46%, as confirmed by means of MTT, western blot, flow cytometry, and CLSM. Significantly, by using one intravenous injection of PNOC-PDA/DOX and a single NIR irradiation, the triple therapies of mild PTT, NO gas therapy, and CT achieved complete MCF-7/ADR tumor ablation without skin damage, scarring, and tumor recurrence within 30 days. This work provides a versatile method for the fabrication of NIR-responsive polypeptide nanocomposite with intrinsic photothermal conversion and NO-releasing attributes, opening up a new avenue for reversing MDR in tumor.