Motor neurons generate pose-targeted movements via proprioceptive sculpting.

Motor neurons are the final common pathway1 through which the brain controls movement of the body, forming the basic elements from which all movement is composed. Yet how a single motor neuron contributes to control during natural movement remains unclear. Here we anatomically and functionally characterize the individual roles of the motor neurons that control head movement in the fly, Drosophila melanogaster. Counterintuitively, we find that activity in a single motor neuron rotates the head in different directions, depending on the starting posture of the head, such that the head converges towards a pose determined by the identity of the stimulated motor neuron. A feedback model predicts that this convergent behaviour results from motor neuron drive interacting with proprioceptive feedback. We identify and genetically2 suppress a single class of proprioceptive neuron3 that changes the motor neuron-induced convergence as predicted by the feedback model. These data suggest a framework for how the brain controls movements: instead of directly generating movement in a given direction by activating a fixed set of motor neurons, the brain controls movements by adding bias to a continuing proprioceptive-motor loop.

Role of Titanium Dioxide-Immobilized PES Beads in a Combined Water Treatment System of Tubular Alumina Microfiltration and PES Beads.

The membrane process has a limit to the decay of various pollutants in water. To improve the problem, the roles of backwashing media and titanium dioxide (TiO2) photocatalyst-immobilized-polyethersulfone (PES) beads' concentration were investigated in a combined system of tubular alumina MF and the PES beads for advanced drinking water treatment. The space between the outside of the MF membrane and the module inside was filled with the PES beads. UV at a wavelength of 352 nm was irradiated from outside of the acryl module. A quantity of humic acid and kaolin was dissolved in distilled water for synthetic water. Water or air intermittent backwashing was performed outside to inside. The membrane fouling resistance after 3 h process (Rf,180) was minimum at 30 g/L of the PES beads for water backwashing, and at 40 g/L for air backwashing when increasing the PES beads from 0 to 50 g/L. The irreversible membrane fouling resistance after physical cleaning (Rif) was at the bottom at 5 g/L of the PES beads for water backwashing, which was 3.43 times higher than minimal at 40 g/L of the PES beads for air backwashing. The treatment effectiveness of turbidity increased when increasing the PES beads' concentration from 0 to 50 g/L; however, it reached a maximum at 98.1% at 40 g/L and 99.2% at 50 g/L for water and air backwashing, respectively. The treatment effectiveness of UV254 absorbance, which was dissolved organic matter (DOM), increased dramatically when increasing the PES beads; however, it reached a peak of 83.0% at 40 g/L and 86.0% at 50 g/L for water and air backwashing, respectively. Finally, the best PES beads' concentration was 20~30 g/L to minimize the membrane fouling; however, it was 50 g/L to remove pollutants effectively. The water backwashing was better than the air at treating DOM; however, the air backwashing was more effective than the water at removing turbid matter and reducing membrane fouling.

Synaptic gradients transform object location to action.

To survive, animals must convert sensory information into appropriate behaviours1,2. Vision is a common sense for locating ethologically relevant stimuli and guiding motor responses3-5. How circuitry converts object location in retinal coordinates to movement direction in body coordinates remains largely unknown. Here we show through behaviour, physiology, anatomy and connectomics in Drosophila that visuomotor transformation occurs by conversion of topographic maps formed by the dendrites of feature-detecting visual projection neurons (VPNs)6,7 into synaptic weight gradients of VPN outputs onto central brain neurons. We demonstrate how this gradient motif transforms the anteroposterior location of a visual looming stimulus into the fly's directional escape. Specifically, we discover that two neurons postsynaptic to a looming-responsive VPN type promote opposite takeoff directions. Opposite synaptic weight gradients onto these neurons from looming VPNs in different visual field regions convert localized looming threats into correctly oriented escapes. For a second looming-responsive VPN type, we demonstrate graded responses along the dorsoventral axis. We show that this synaptic gradient motif generalizes across all 20 primary VPN cell types and most often arises without VPN axon topography. Synaptic gradients may thus be a general mechanism for conveying spatial features of sensory information into directed motor outputs.

Sources and sequestration rate of organic carbon in sediments of the bare tidal flat ecosystems: A model approach.

Humans have been contributing adversely to greenhouse gas emissions by generating a vast amount of CO2, primarily causing climate change. Nature-based climate solutions, consisting of both terrestrial and marine ecosystems, are tremendous potential for sequestering and storing significant amounts of carbon, which can help to slow the progression of climate change. In this study, we use a carbon balance model to simulate the carbon sequestration rate and carbon stored in bare tidal flat (BTF) areas along Korea's west and south coasts from 2018 to 2050. Furthermore, the percentage of potential carbon sources deposited at BTF sites was calculated using a two-terminal mixing model and δ13C data. The carbon deposited on the BTF areas is the result of lateral carbon transport from upslope terrestrial regions as well as marine sources. Based on the δ13C isotope, this study classified potential carbon sources in BTFs sediment into two categories: terrestrial and marine. The results indicate that the proportion of organic carbon contribution from terrestrial sources ranged from 7.63% to 49% in the BTF studied areas. We discuss the validity of projection which was investigated over three years, from 2018 to 2020. A preliminary conclusion is that future carbon storage at BTF sites will increase significantly. Carbon accumulation increases linearly over time in nearly all areas studied, with carbon sequestration rates ranging from 0.053 to 0.623 (MgC ha-1 yr-1). This study found that a significant amount of carbon is sequestered for a long time in the BTF regions based on model simulation results. In addition, it also contributes to projects that seek to promote and conserve these climate benefits by providing estimates of carbon storage in coastal BTFs that can be included in NDCs for the Paris Agreement.

Healing Ion-Implanted Semiconductors by Hybrid Microwave Annealing: Activation of Nitrogen-Implanted TiO2.

In order to recover the damaged structure of a nitrogen-implanted TiO2 (N-I-TiO2) photoanode, hybrid microwave annealing (HMA) is proposed as an alternative postannealing process instead of conventional thermal annealing (CTA). Compared to CTA, HMA provides distinctive advantages: (i) facile transformation of the interstitial N-N states into substitutional N-Ti states, (ii) better preservation of the ion-implanted nitrogen in TiO2, and (iii) effective alleviation of lattice strain and reconstruction of the broken bonds. As a result, the HMA-activated photoanode improves the photocurrent density by a factor of ∼3.2 from 0.29 to 0.93 mA cm-2 at 1.23 VRHE and the incident photon-to-current conversion efficiency (IPCE) from ∼2.9% to ∼10.5% at 430 nm relative to those of the as-prepared N-I-TiO2 photoanode in photoelectrochemical water oxidation, which are much better than those of the CTA-activated photoanode (0.58 mA cm-2 at 1.23 VRHE and IPCE of 5.7% at 430 nm), especially in the visible light region (≥420 nm).

Optimal Water Backwashing Condition in Combined Water Treatment of Alumina Microfiltration and PP Beads.

Membrane fouling is a dominant limit of the membrane separation process. In this research, the optimal water backwashing to solve the membrane fouling problem was investigated in the combined water treatment process of alumina MF and pure polypropylene (PP) beads. Additionally, the influence of membrane shape (tubular or seven channel) was examined, depending on the water backwashing period. The optimal backwashing time (BT) could be 20 s in the combined water treatment process, because of the highest total treated volume (VT) in our BT 6-30 s conditions. The optimal backwashing period (BP) could be 6 min, because of the minimum membrane fouling and the maximum VT in the combined process of tubular alumina MF and PP beads. The resistance of reversible membrane fouling (Rrf) showed a major resistance of total membrane fouling, and that of irreversible membrane fouling (Rif) was a minor one, in the combined process using tubular or seven channel MF. The Rif showed a decreasing trend obviously, as decreasing BT from NBW to 2 min for seven channel MF. It means that the more frequent water backwashing could be more effective to control the membrane fouling, especially irreversible fouling, for seven channel membranes than tubular membranes.

A Preclinical Trial and Molecularly Annotated Patient Cohort Identify Predictive Biomarkers in Homologous Recombination-deficient Pancreatic Cancer.

PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) arising in patients with a germline BRCA1 or BRCA2 (gBRCA) mutation may be sensitive to platinum and PARP inhibitors (PARPi). However, treatment stratification based on gBRCA mutational status alone is associated with heterogeneous responses. EXPERIMENTAL DESIGN: We performed a seven-arm preclinical trial consisting of 471 mice, representing 12 unique PDAC patient-derived xenografts, of which nine were gBRCA mutated. From 179 patients whose PDAC was whole-genome and transcriptome sequenced, we identified 21 cases with homologous recombination deficiency (HRD), and investigated prognostic biomarkers. RESULTS: We found that biallelic inactivation of BRCA1/BRCA2 is associated with genomic hallmarks of HRD and required for cisplatin and talazoparib (PARPi) sensitivity. However, HRD genomic hallmarks persisted in xenografts despite the emergence of therapy resistance, indicating the presence of a genomic scar. We identified tumor polyploidy and a low Ki67 index as predictors of poor cisplatin and talazoparib response. In patients with HRD PDAC, tumor polyploidy and a basal-like transcriptomic subtype were independent predictors of shorter survival. To facilitate clinical assignment of transcriptomic subtype, we developed a novel pragmatic two-marker assay (GATA6:KRT17). CONCLUSIONS: In summary, we propose a predictive and prognostic model of gBRCA-mutated PDAC on the basis of HRD genomic hallmarks, Ki67 index, tumor ploidy, and transcriptomic subtype.

Concurrent Formation of N-H Imines and Carbonyl Compounds by Ruthenium-Catalyzed C-C Bond Cleavage of ß-Hydroxy Azides.

A commercial cyclopentadienylrutenium dicarbonyl dimer ([CpRu(CO)2]2) efficiently catalyzes the formation of N-H imines and carbonyl compounds simultaneously from ß-hydroxy azides via C-C bond cleavage under visible light. Density functional theory calculations for the cleavage reaction support the mechanism involving chelation of alkoxy azide species and liberation of nitrogen as the driving force. The synthetic utility of the reaction was demonstrated by a new amine synthesis promoted by chemoselective allylation of imine and synthesis of isoquinoline.

The Function of Adsorption, Photo-Oxidation, and Humic Acid Using Air Backwashing in Integrated Water Treatment of Multichannel Ceramic MF and PP Particles.

For advanced water treatment, function of microfiltration (MF), adsorption, photo-oxidation, humic acid (HA), and polypropylene (PP) particles on membrane fouling and decay effectiveness were investigated in an integrated water treatment, of multichannel ceramic MF and PP particles, using UV radiation and air backwashing. The synthetic feed was organized with HA and kaolin. The membrane fouling resistance (Rf) of the (MF + PP) system presented the lowermost, and amplified intensely from the (MF + UV) to MF system. The percentages of MF and adsorption by PP particles for turbidity treatment were 87.6% and 3.8%, individually; however, the percentages of MF and adsorption by PP particles for dissolved organic matters (DOM) treatment were 27.9% and 5.0%, respectively. The decay effectiveness of turbidity presented the greatest 95.4% at HA of 10 mg/L; however, that of DOM increased as HA concentration ascended. The ultimate Rf after 180 min procedure showed the maximum at 30 g/L of PP particles concentration, and improved dramatically, as PP particles decreased. Finally, the maximum VT was acquired at 30 and 50 g/L of PP particles, because flux preserved greater throughout the procedure. The decay effectiveness of turbidity and DOM showed the maximal 95.4% and 56.8% at 40 and 50 g/L of PP particles, respectively.

The Role of Humic Acid, PP Beads, and pH with Water Backwashing in a Hybrid Water Treatment of Multichannel Alumina Microfiltration and PP Beads.

Photooxidation oxidizes most organic compounds by mineralizing them to small inorganic molecules. In this study, the effects of dissolved organic matter (DOM), pH, and polypropylene (PP) beads concentration on membrane fouling were investigated in a hybrid water treatment process consisting of seven-channel alumina microfiltration (pore size 1.0 µm) and pure PP beads water backwashing with UV irradiation for photooxidation. The synthetic feed was prepared with humic acid and kaolin and flowed inside the microfiltration (MF) membrane. The permeate contacted the PP beads fluidized in the gap of the membrane and module with outside UV irradiation. Membrane fouling resistance (Rf) increased dramatically with an increase in the concentration of humic acid (HA) from 6 mg/L to 8 mg/L. The treatment efficiency of DOM increased dramatically, from 14.3% to 49.7%, with an increase in the concentration of HA. The Rf decreased with an increase of PP beads concentration. However, maximum permeate volume (VT) was acquired at 5 g/L of PP beads. The maximal treatment efficiency of DOM was 51.3% at 40 g/L of PP beads. The Rf increased with an increase in the pH of feed, and the maximum VT was acquired at a pH of 5. The maximal treatment efficiency of DOM was 52.5% at pH 9.

Base-Free Dynamic Kinetic Resolution of Secondary Alcohols with a Ruthenium-Lipase Couple.

We report the dynamic kinetic resolution (DKR) of various secondary alcohols by the combination of a ruthenium catalyst and an anionic surfactant-activated lipoprotein lipase. The DKR reactions performed under totally base-free conditions at room temperature provided the products of excellent enantiopurities (91-99% ee or greater) in high yields (92-99%). More importantly, the DKR of α-arylallyl alcohols was achieved for the first time with high yields (87-91%).

Effect of pH and polypropylene beads in hybrid water treatment process of alumina ceramic microfiltration and PP beads with air back-flushing and UV irradiation.

For advanced water treatment, effects of pH and pure polypropylene (PP) beads packing concentration on membrane fouling and treatment efficiency were observed in a hybrid process of alumina ceramic microfiltration (MF; pore size 0.1 µm) and pure PP beads. Instead of natural organic matters and fine inorganic particles in natural water source, a quantity of humic acid (HA) and kaolin was dissolved in distilled water. The synthetic feed flowed inside the MF membrane, and the permeated water contacted the PP beads fluidized in the gap of the membrane and the acryl module case with outside UV irradiation. Periodic air back-flushing was performed to control membrane fouling during 10 s per 10 min. The membrane fouling resistance (Rf) was the maximum at 30 g/L of PP bead concentration. Finally, the maximum total permeated volume (VT) was acquired at 5 g/L of PP beads, because flux maintained higher all through the operation. The treatment efficiency of turbidity was almost constant, independent of PP bead concentration; however, that of dissolved organic materials (DOM) showed the maximal at 50 g/L of PP beads. The Rf increased as increasing feed pH from 5 to 9; however, the maximum VT was acquired at pH 6. It means that the membrane fouling could be inhibited at low acid condition. The treatment efficiency of turbidity increased a little, and that of DOM increased from 73.6 to 75.7% as increasing pH from 5 to 9.

Methyllucidone inhibits STAT3 activity by regulating the expression of the protein tyrosine phosphatase MEG2 in DU145 prostate carcinoma cells.

During the search for signal transducer and activator of transcription 3 (STAT3) inhibitors from natural products, methyllucidone, isolated from Lindera species (Lauraceae), was identified as a STAT3 inhibitor. Methyllucidone inhibited STAT3 phosphorylation at tyrosine 705 in a dose- and time dependent manner in DU145 prostate cancer cells and suppressed IL-6-induced STAT3 phosphorylation at Tyr-705 in LNCaP cells. Methyllucidone decreased the expression levels of STAT3 target genes, such as cyclin D1, cyclin A, Bcl-2, Mcl-1, and survivin. Methyllucidone inhibited DU145 cell growth and induced apoptosis by arresting the cell cycle at G1 phase. Notably, knockdown of the MEG2 gene by small interfering RNA suppressed the ability of methyllucidone to inhibit STAT3 activation. Methyllucidone regulates STAT3 activity by modulating MEG2 expression, and our results suggest that this compound is a novel inhibitor of the STAT3 pathway and may be a useful lead molecule for the development of a therapeutic STAT3 inhibitor.

Cytokine Response to Diet and Exercise Affects Atheromatous Matrix Metalloproteinase-2/9 Activity in Mice.

BACKGROUND: The aim of this study is to identify the principal circulating factors that modulate atheromatous matrix metalloproteinase (MMP) activity in response to diet and exercise.Methods and Results:Apolipoprotein-E knock-out (ApoE-/-) mice (n=56) with pre-existing plaque, fed either a Western diet (WD) or normal diet (ND), underwent either 10 weeks of treadmill exercise or had no treatment. Atheromatous MMP activity was visualized using molecular imaging with a MMP-2/9 activatable near-infrared fluorescent (NIRF) probe. Exercise did not significantly reduce body weight, visceral fat, and plaque size in either WD-fed animals or ND-fed animals. However, atheromatous MMP-activity was different; ND animals that did or did not exercise had similarly low MMP activities, WD animals that did not exercise had high MMP activity, and WD animals that did exercise had reduced levels of MMP activity, close to the levels of ND animals. Factor analysis and path analysis showed that soluble vascular cell adhesion molecule (sVCAM)-1 was directly positively correlated to atheromatous MMP activity. Adiponectin was indirectly negatively related to atheromatous MMP activity by way of sVCAM-1. Resistin was indirectly positively related to atheromatous MMP activity by way of sVCAM-1. Visceral fat amount was indirectly positively associated with atheromatous MMP activity, by way of adiponectin reduction and resistin elevation. MMP-2/9 imaging of additional mice (n=18) supported the diet/exercise-related anti-atherosclerotic roles for sVCAM-1. CONCLUSIONS: Diet and exercise affect atheromatous MMP activity by modulating the systemic inflammatory milieu, with sVCAM-1, resistin, and adiponectin closely interacting with each other and with visceral fat.

Ca2+ Regulation of Cav3.3 T-type Ca2+ Channel Is Mediated by Calmodulin.

Calcium-dependent inactivation of high voltage-activated Ca2+ channels plays a crucial role in limiting rises in intracellular calcium (Ca2+i). A key mediator of these effects is calmodulin, which has been found to bind the C-terminus of the pore-forming α subunit. In contrast, little is known about how Ca2+i can regulate low voltage-activated T-type Ca2+ channels. Using whole cell patch clamp, we examined the biophysical properties of Ca2+ current through the three T-type Ca2+ channel isoforms, Cav3.1, Cav3.2, or Cav3.3, comparing internal solutions containing 27 nM and l µM free Ca2+ Both activation and inactivation kinetics of Cav3.3 current in l µM Ca2+i solution were more rapid than those in 27 nM Ca2+i solution. In addition, both activation and steady-state inactivation curves of Cav3.3 were negatively shifted in the higher Ca2+i solution. In contrast, the biophysical properties of Cav3.1 and Cav3.2 isoforms were not significantly different between the two internal solutions. Overexpression of CaM1234 (a calmodulin mutant that doesn't bind Ca2+) occluded the effects of l µM Ca2+i on Cav3.3, implying that CaM is involved in the Ca2+i regulation effects on Cav3.3. Yeast two-hybrid screening and co-immunoprecipitation experiments revealed a direct interaction of CaM with the carboxyl terminus of Cav3.3. Taken together, our results suggest that Cav3.3 T-type channel is potently regulated by Ca2+i via interaction of Ca2+/CaM with the carboxyl terminus of Cav3.3.

Drosophila SLC5A11 Mediates Hunger by Regulating K(+) Channel Activity.

Hunger is a powerful drive that stimulates food intake. Yet, the mechanism that determines how the energy deficits that result in hunger are represented in the brain and promote feeding is not well understood. We previously described SLC5A11-a sodium/solute co-transporter-like-(or cupcake) in Drosophila melanogaster, which is required for the fly to select a nutritive sugar over a sweeter nonnutritive sugar after periods of food deprivation. SLC5A11 acts on approximately 12 pairs of ellipsoid body (EB) R4 neurons to trigger the selection of nutritive sugars, but the underlying mechanism is not understood. Here, we report that the excitability of SLC5A11-expressing EB R4 neurons increases dramatically during starvation and that this increase is abolished in the SLC5A11 mutation. Artificial activation of SLC5A11-expresssing neurons is sufficient to promote feeding and hunger-driven behaviors; silencing these neurons has the opposite effect. Notably, SLC5A11 transcript levels in the brain increase significantly when flies are starved and decrease shortly after starved flies are refed. Furthermore, expression of SLC5A11 is sufficient for promoting hunger-driven behaviors and enhancing the excitability of SLC5A11-expressing neurons. SLC5A11 inhibits the function of the Drosophila KCNQ potassium channel in a heterologous expression system. Accordingly, a knockdown of dKCNQ expression in SLC5A11-expressing neurons produces hunger-driven behaviors even in fed flies, mimicking the overexpression of SLC5A11. We propose that starvation increases SLC5A11 expression, which enhances the excitability of SLC5A11-expressing neurons by suppressing dKCNQ channels, thereby conferring the hunger state.

Nitrogen ion implantation into various materials using 28 GHz electron cyclotron resonance ion source.

The installation of the 28 GHz electron cyclotron resonance ion source (ECRIS) ion implantation beamline was recently completed at the Korea Basic Science Institute. The apparatus contains a beam monitoring system and a sample holder for the ion implantation process. The new implantation system can function as a multipurpose tool since it can implant a variety of ions, ranging hydrogen to uranium, into different materials with precise control and with implantation areas as large as 1-10 mm(2). The implantation chamber was designed to measure the beam properties with a diagnostic system as well as to perform ion implantation with an in situ system including a mass spectrometer. This advanced implantation system can be employed in novel applications, including the production of a variety of new materials such as metals, polymers, and ceramics and the irradiation testing and fabrication of structural and functional materials to be used in future nuclear fusion reactors. In this investigation, the first nitrogen ion implantation experiments were conducted using the new system. The 28 GHz ECRIS implanted low-energy, multi-charged nitrogen ions into copper, zinc, and cobalt substrates, and the ion implantation depth profiles were obtained. SRIM 2013 code was used to calculate the profiles under identical conditions, and the experimental and simulation results are presented and compared in this report. The depths and ranges of the ion distributions in the experimental and simulation results agree closely and demonstrate that the new system will enable the treatment of various substrates for advanced materials research.

First results of 28 GHz superconducting electron cyclotron resonance ion source for KBSI accelerator.

The 28 GHz superconducting electron cyclotron resonance (ECR) ion source has been developed to produce a high current heavy ion for the linear accelerator at KBSI (Korea Basic Science Institute). The objective of this study is to generate fast neutrons with a proton target via a p(Li,n)Be reaction. The design and fabrication of the essential components of the ECR ion source, which include a superconducting magnet with a liquid helium re-condensed cryostat and a 10 kW high-power microwave, were completed. The waveguide components were connected with a plasma chamber including a gas supply system. The plasma chamber was inserted into the warm bore of the superconducting magnet. A high voltage system was also installed for the ion beam extraction. After the installation of the ECR ion source, we reported the results for ECR plasma ignition at ECRIS 2014 in Russia. Following plasma ignition, we successfully extracted multi-charged ions and obtained the first results in terms of ion beam spectra from various species. This was verified by a beam diagnostic system for a low energy beam transport system. In this article, we present the first results and report on the current status of the KBSI accelerator project.