The Gene-Silencing Protein MORC-1 Topologically Entraps DNA and Forms Multimeric Assemblies to Cause DNA Compaction.

Microrchidia (MORC) ATPases are critical for gene silencing and chromatin compaction in multiple eukaryotic systems, but the mechanisms by which MORC proteins act are poorly understood. Here, we apply a series of biochemical, single-molecule, and cell-based imaging approaches to better understand the function of the Caenorhabditis elegans MORC-1 protein. We find that MORC-1 binds to DNA in a length-dependent but sequence non-specific manner and compacts DNA by forming DNA loops. MORC-1 molecules diffuse along DNA but become static as they grow into foci that are topologically entrapped on DNA. Consistent with the observed MORC-1 multimeric assemblies, MORC-1 forms nuclear puncta in cells and can also form phase-separated droplets in vitro. We also demonstrate that MORC-1 compacts nucleosome templates. These results suggest that MORCs affect genome structure and gene silencing by forming multimeric assemblages to topologically entrap and progressively loop and compact chromatin.

Highly Exposed NH2 Edge on Fragmented g-C3 N4 Framework with Integrated Molybdenum Atoms for Catalytic CO2 Cycloaddition: DFT and Techno-Economic Assessment.

This study focuses on the applicability of single-atom Mo-doped graphitic carbon nitride (GCN) nanosheets which are specifically engineered with high surface area (exfoliated GCN), NH2 rich edges, and maximum utilization of isolated atomic Mo for propylene carbonate (PC) production through CO2 cycloaddition of propylene oxide (PO). Various operational parameters are optimized, for example, temperature (130 °C), pressure (20 bar), catalyst (Mo2 GCN), and catalyst mass (0.1 g). Under optimal conditions, 2% Mo-doped GCN (Mo2 GCN) has the highest catalytic performance, especially the turnover frequency (TOF) obtained, 36.4 h-1 is higher than most reported studies. DFT simulations prove the catalytic performance of Mo2 GCN significantly decreases the activation energy barrier for PO ring-opening from 50-60 to 4.903 kcal mol-1 . Coexistence of Lewis acid/base group improves the CO2 cycloaddition performance by the formation of coordination bond between electron-deficient Mo atom with O atom of PO, while NH2 surface group disrupts the stability of CO2 bond by donating electrons into its low-level empty orbital. Steady-state process simulation of the industrial-scale consumes 4.4 ton h-1 of CO2 with PC production of 10.2 ton h-1 . Techno-economic assessment profit from Mo2 GCN is estimated to be 60.39 million USD year-1 at a catalyst loss rate of 0.01 wt% h-1 .

Remarkable Electrical Conductivity Increase and Pure Metallic Properties from Semiconducting Colloidal Nanocrystals by Cation Exchange for Solution-Processable Optoelectronic Applications.

The authors report a strategic approach to achieve metallic properties from semiconducting CuFeS colloidal nanocrystal (NC) solids through cation exchange method. An unprecedentedly high electrical conductivity is realized by the efficient generation of charge carriers onto a semiconducting CuS NC template via minimal Fe exchange. An electrical conductivity exceeding 10 500 S cm-1 (13 400 S cm-1 at 2 K) and a sheet resistance of 17 Ω/sq at room temperature, which are among the highest values for solution-processable semiconducting NCs, are achieved successfully from bornite-phase CuFeS NC films possessing 10% Fe atom. The temperature dependence of the corresponding films exhibits pure metallic characteristics. Highly conducting NCs are demonstrated for a thermoelectric layer exhibiting a high power factor over 1.2 mW m-1 K-2 at room temperature, electrical wires for switching on light emitting diods (LEDs), and source-drain electrodes for p- and n-type organic field-effect transistors. Ambient stability, eco-friendly composition, and solution-processability further validate their sustainable and practical applicability. The present study provides a simple but very effective method for significantly increasing charge carrier concentrations in semiconducting colloidal NCs to achieve metallic properties, which is applicable to various optoelectronic devices.

Conductive and Ultrastable Covalent Organic Framework/Carbon Hybrid as an Ideal Electrocatalytic Platform.

Developing covalent organic frameworks (COFs) with good electrical conductivity is essential to widen their range of practical applications. Thermal annealing is known to be a facile approach for enhancing conductivity. However, at higher temperatures, most COFs undergo amorphization and/or thermal degradation because of the lack of linker rigidity and physicochemical stability. Here, we report the synthesis of a conductive benzoxazole-linked COF/carbon hybrid material (BCOF-600C) by simple thermal annealing. The fused-aromatic benzoxazole and biphenyl building units endow the resulting COF with excellent physicochemical stability against high temperatures and strong acids/bases. This allows heat treatment to further enhance electrical conductivity with minimal structural alteration. The robust crystalline structure with periodically incorporated nitrogen atoms allowed platinum (Pt) atoms to be atomically integrated into the channel walls of BCOF-600C. The resulting electrocatalyst with well-defined active sites exhibited superior catalytic performance toward hydrogen evolution in acidic media.

Multispectral Benchmark Dataset and Baseline for Forklift Collision Avoidance.

In this paper, multispectral pedestrian detection is mainly discussed, which can contribute to assigning human-aware properties to automated forklifts to prevent accidents, such as collisions, at an early stage. Since there was no multispectral pedestrian detection dataset in an intralogistics domain, we collected a dataset; the dataset employs a method that aligns image pairs with different domains, i.e. RGB and thermal, without the use of a cumbersome device such as a beam splitter, but rather by exploiting the disparity between RGB sensors and camera geometry. In addition, we propose a multispectral pedestrian detector called SSD 2.5D that can not only detect pedestrians but also estimate the distance between an automated forklift and workers. In extensive experiments, the performance of detection and centroid localization is validated with respect to evaluation metrics used in the driving car domain but with distinct categories, such as hazardous zone and warning zone, to make it more applicable to the intralogistics domain.

Identification and characterization of bisbenzimide compounds that inhibit human cytomegalovirus replication.

The shortcomings of current anti-human cytomegalovirus (HCMV) drugs has stimulated a search for anti-HCMV compounds with novel targets. We screened collections of bioactive compounds and identified a range of compounds with the potential to inhibit HCMV replication. Of these compounds, we selected bisbenzimide compound RO-90-7501 for further study. We generated analogues of RO-90-7501 and found that one compound, MRT00210423, had increased anti-HCMV activity compared to RO-90-7501. Using a combination of compound analogues, microscopy and biochemical assays we found RO-90-7501 and MRT00210423 interacted with DNA. In single molecule microscopy experiments we found RO-90-7501, but not MRT00210423, was able to compact DNA, suggesting that compaction of DNA was non-obligatory for anti-HCMV effects. Using bioinformatics analysis, we found that there were many putative bisbenzimide binding sites in the HCMV DNA genome. However, using western blotting, quantitative PCR and electron microscopy, we found that at a concentration able to inhibit HCMV replication our compounds had little or no effect on production of certain HCMV proteins or DNA synthesis, but did have a notable inhibitory effect on HCMV capsid production. We reasoned that these effects may have involved binding of our compounds to the HCMV genome and/or host cell chromatin. Therefore, our data expand our understanding of compounds with anti-HCMV activity and suggest targeting of DNA with bisbenzimide compounds may be a useful anti-HCMV strategy.

Toll-like receptor 2 promotes neurogenesis from the dentate gyrus after photothrombotic cerebral ischemia in mice.

The subgranular zone (SGZ) of hippocampal dentate gyrus (HDG) is a primary site of adult neurogenesis. Toll-like receptors (TLRs), are involved in neural system development of Drosophila and innate immune response of mammals. TLR2 is expressed abundantly in neurogenic niches such as adult mammalian hippocampus. It regulates adult hippocampal neurogenesis. However, the role of TLR2 in adult neurogenesis is not well studied in global or focal cerebral ischemia. Therefore, this study aimed to investigate the role of TLR2 in adult neurogenesis after photochemically induced cerebral ischemia. At 7 days after photothrombotic ischemic injury, the number of bromodeoxyuridine (BrdU)-positive cells was increased in both TLR2 knock-out (KO) mice and wild-type (WT) mice. However, the increment rate of BrdU-positive cells was lower in TLR2 KO mice compared to that in WT mice. The number of doublecortin (DCX) and neuronal nuclei (NeuN)-positive cells in HDG was decreased after photothrombotic ischemia in TLR2 KO mice compared to that in WT mice. The survival rate of cells in HDG was decreased in TLR2 KO mice compared to that in WT mice. In contrast, the number of cleaved-caspase 3 (apoptotic marker) and the number of GFAP (glia marker)/BrdU double-positive cells in TLR2 KO mice were higher than that in WT mice. These results suggest that TLR2 can promote adult neurogenesis from neural stem cell of hippocampal dentate gyrus through increasing proliferation, differentiation, and survival from neural stem cells after ischemic injury of the brain.

Myosin VI dimerization triggers an unfolding of a three-helix bundle in order to extend its reach.

Myosin VI challenges the prevailing theory of how myosin motors move on actin: the lever arm hypothesis. While the reverse directionality and large powerstroke of myosin VI can be attributed to unusual properties of a subdomain of the motor (converter with a unique insert), these adaptations cannot account for the large step size on actin. Either the lever arm hypothesis needs modification, or myosin VI has some unique form of extension of its lever arm. We determined the structure of the region immediately distal to the lever arm of the motor and show that it is a three-helix bundle. Based on C-terminal truncations that display the normal range of step sizes on actin, CD, fluorescence studies, and a partial deletion of the bundle, we demonstrate that this bundle unfolds upon dimerization of two myosin VI monomers. This unconventional mechanism generates an extension of the lever arm of myosin VI.

The Effect of the Lacticaseibacillus paracasei BEPC22 and Lactiplantibacillus plantarum BELP53 Combination (BN-202M) on Body Fat Percentage Loss in Overweight Individuals: A Randomized, Double-Blind, Placebo-Controlled Study.

BN-202M is derived from humans and consists of two strains, Lacticaseibacillus paracasei BEPC22 and Lactiplantibacillus plantarum BELP53. Body fat reduction effect and safety of BN-202M were assessed in overweight participants. A total of 150 participants were randomly assigned to the BN-202M and placebo groups at a 1:1 ratio. Dual-energy X-ray absorptiometry was used to objectively measure body fat. After 12 weeks of oral administration, the body fat percentage (-0.10 ± 1.32% vs. 0.48 ± 1.10%; p = 0.009) and body fat mass (-0.24 ± 1.19 kg vs. 0.23 ± 1.05 kg; p = 0.023) of the BN-202M group decreased significantly compared to those of the placebo group. The body weight (-0.58 kg, p = 0.004) and body mass index (BMI; -0.23, p = 0.003) was found to decrease significantly at 12 weeks in the BN-202M group, but not in the placebo group. Metabolome analysis revealed that ß-alanine, 3-aminoisobutyric acid, glutamic acid, and octopamine decreased in the weight-decreased BN-202M post-intake group. In the gut microbiota analysis, Akkermansia showed a statistically significant increase in the BN-202M group post-intake compared to the placebo group. No serious adverse events were observed in either group. These results suggest that BN-202M is safe and effective for reducing body fat and weight.

Multicolor super-resolution DNA imaging for genetic analysis.

Many types of cancer and neurodegenerative diseases are caused by abnormalities and variations in the genome. We have designed a high-resolution imaging technique with high throughput and low cost for determining structural variations of genes related to genetic diseases. We initially mapped all seven nicking sites of Nb.BbvCI endonuclease enzyme on lambda DNA. Then we resolved densely labeled patterns of 107 nicking sites on human BAC DNA that is digested by Nb.BsmI and Nb.BbvCI endonuclease enzymes. This high density resulted in several dyes being closer together than the diffraction limit. Overall, detailed DNA nicking sites mapping with 100 bp resolution was achieved, which has the potential to reveal information about genetic variance and to facilitate medical diagnosis of several genetic diseases.

Tactile Neuromorphic System: Convergence of Triboelectric Polymer Sensor and Ferroelectric Polymer Synapse.

Sensory neuromorphic systems are a promising technology, because they can replicate the way the human peripheral nervous system processes signals from the five sensory organs. Despite this potential, there are limited studies on how to implement these systems on a hardware neural network platform. In our research, we propose a tactile neuromorphic system that uses a poly(dimethylsiloxane) (PDMS)-based triboelectric sensor and a molybdenum disulfide (MoS2)/poly(vinylidene fluoride-trifluoro ethylene) (P(VDF-TrFE)) heterostructure-based ferroelectric synapse. The triboelectric sensor mimics a human tactile organ by converting tactile stimuli into electrical signals in real time. The ferroelectric synapse we developed demonstrates exceptional long-term potentiation/depression characteristics with a maximum dynamic range of 78 and a symmetrical value of 4.7. To assess the practicality of our proposed system, we conducted training and recognition simulations using Morse code alphabets and MNIST handwritten digits. The maximum recognition rate that we achieved was 96.17%.

Using DNA flow-stretching assay as a tool to validate the tagging of DNA-binding proteins for single-molecule experiments.

Due to the enhanced labeling capability of maleimide-based fluorescent probes, lysine-cysteine-lysine (KCK) tags are frequently added to proteins for visualization. In this study, we employed in vitro single-molecule DNA flow-stretching assay as a sensitive way to assess the impact of the KCK-tag on the property of DNA-binding proteins. Using Bacillus subtilis ParB as an example, we show that, although no noticeable changes were detected by in vivo fluorescence imaging and chromatin immunoprecipitation (ChIP) assays, the KCK-tag substantially altered ParB's DNA compaction rates, its response to nucleotide binding and to the presence of the specific sequence (parS) on the DNA. While it is typically assumed that short peptide tags minimally perturb protein function, our results urge researchers to carefully validate the use of tags for protein labeling. Our comprehensive analysis can be expanded and used as a guide to assess the impacts of other tags on DNA-binding proteins in single-molecule assays.

Learning quadrupedal locomotion on deformable terrain.

Simulation-based reinforcement learning approaches are leading the next innovations in legged robot control. However, the resulting control policies are still not applicable on soft and deformable terrains, especially at high speed. The primary reason is that reinforcement learning approaches, in general, are not effective beyond the data distribution: The agent cannot perform well in environments that it has not experienced. To this end, we introduce a versatile and computationally efficient granular media model for reinforcement learning. Our model can be parameterized to represent diverse types of terrain from very soft beach sand to hard asphalt. In addition, we introduce an adaptive control architecture that can implicitly identify the terrain properties as the robot feels the terrain. The identified parameters are then used to boost the locomotion performance of the legged robot. We applied our techniques to the Raibo robot, a dynamic quadrupedal robot developed in-house. The trained networks demonstrated high-speed locomotion capabilities on deformable terrains: The robot was able to run on soft beach sand at 3.03 meters per second although the feet were completely buried in the sand during the stance phase. We also demonstrate its ability to generalize to different terrains by presenting running experiments on vinyl tile flooring, athletic track, grass, and a soft air mattress.

A framework to validate fluorescently labeled DNA-binding proteins for single-molecule experiments.

Due to the enhanced labeling capability of maleimide-based fluorescent probes, lysine-cysteine-lysine (KCK) tags are frequently added to proteins for visualization. In this study, we employed an in vitro single-molecule DNA flow-stretching assay as a sensitive way to assess the impact of the KCK tag on the property of DNA-binding proteins. Using Bacillus subtilis ParB as an example, we show that, although no noticeable changes were detected by in vivo fluorescence imaging and chromatin immunoprecipitation (ChIP) assays, the KCK tag substantially altered ParB's DNA compaction rates and its response to nucleotide binding and to the presence of the specific sequence (parS) on the DNA. While it is typically assumed that short peptide tags minimally perturb protein function, our results urge researchers to carefully validate the use of tags for protein labeling. Our comprehensive analysis can be expanded and used as a guide to assess the impacts of other tags on DNA-binding proteins in single-molecule assays.

Direct Electrochemical Functionalization of Graphene Grown on Cu Including the Reaction Rate Dependence on the Cu Facet Type.

We present an electrochemical method to functionalize single-crystal graphene grown on copper foils with a (111) surface orientation by chemical vapor deposition (CVD). Graphene on Cu(111) is functionalized with 4-iodoaniline by applying a constant negative potential, and the degree of functionalization depends on the applied potential and reaction time. Our approach stands out from previous methods due to its transfer-free method, which enables more precise and efficient functionalization of single-crystal graphene. We report the suggested effects of the Cu substrate facet by comparing the reactivity of graphene on Cu(111) and Cu(115). The electrochemical reaction rate changes dramatically at the potential threshold for each facet. Kelvin probe force microscopy was used to measure the work function, and the difference in onset potentials of the electrochemical reaction on these two different facets are explained in terms of the difference in work function values. Density functional theory and Monte Carlo calculations were used to calculate the work function of graphene and the thermodynamic stability of the aniline functionalized graphene on these two facets. This study provides a deeper understanding of the electrochemical behavior of graphene (including single-crystal graphene) on Cu(111) and Cu(115). It also serves as a basis for further study of a broad range of reagents and thus functional groups and of the role of metal substrate beneath graphene.

Myosin VI undergoes a 180 degrees power stroke implying an uncoupling of the front lever arm.

We simultaneously measure both the step size, via FIONA, and the 3-D orientation, via DOPI, of the light-chain domain of individual dimeric myosin VIs. This allows for the correlation of the change in orientation of the light chain domain to the stepping of the motor. Three different pairs of positions were tested using a rigid bifunctional rhodamine on the calmodulin of the IQ domain. The data for all three labeling positions support the model that the light chain domain undergoes a significant rotation of approximately 180 degrees . Contrary to an earlier study [Sun, Y. et al. (2007) Mol Cell 28, 954-964], our data does not support a model of multiple angles of the lever arm of the lead head, nor "wiggly" walking on actin. Instead, we propose that for the two heads of myosin VI to coordinate their processive movement, the lever arm of the lead head must be uncoupled from the converter until the rear head detaches. More specifically, intramolecular strain causes the myosin VI lever arm of the lead head to uncouple from the motor domain, allowing the motor domain to go through its product-release (phosphate and ADP) steps at an unstrained rate. The lever arm of the lead head rebinds to the motor and attains a rigor conformation when the rear head detaches. By coupling the orientation and position information with previously described kinetics, this allows us to explain how myosin VI coordinates its heads processively while maintaining the ability to move under load with a (semi-) rigid lever arm.

Digital selective transformation and patterning of highly conductive hydrogel bioelectronics by laser-induced phase separation.

The patterning of poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) hydrogels with excellent electrical property and spatial resolution is a challenge for bioelectronic applications. However, most PEDOT:PSS hydrogels are fabricated by conventional manufacturing processes such as photolithography, inkjet printing, and screen printing with complex fabrication steps or low spatial resolution. Moreover, the additives used for fabricating PEDOT:PSS hydrogels are mostly cytotoxic, thus requiring days of detoxification. Here, we developed a previously unexplored ultrafast and biocompatible digital patterning process for PEDOT:PSS hydrogel via phase separation induced by a laser. We enhanced the electrical properties and aqueous stability of PEDOT:PSS by selective laser scanning, which allowed the transformation of PEDOT:PSS into water-stable hydrogels. PEDOT:PSS hydrogels showed high electrical conductivity of 670 S/cm with 6-µm resolution in water. Furthermore, electrochemical properties were maintained even after 6 months in a physiological environment. We further demonstrated stable neural signal recording and stimulation with hydrogel electrodes fabricated by laser.

Extension of a three-helix bundle domain of myosin VI and key role of calmodulins.

The molecular motor protein myosin VI moves toward the minus-end of actin filaments with a step size of 30-36 nm. Such large step size either drastically limits the degree of complex formation between dimer subunits to leave enough length for the lever arms, or requires an extension of the lever arms' crystallographically observed structure. Recent experimental work proposed that myosin VI dimerization triggers the unfolding of the protein's proximal tail domain which could drive the needed lever-arm extension. Here, we demonstrate through steered molecular dynamics simulation the feasibility of sufficient extension arising from turning a three-helix bundle into a long α-helix. A key role is played by the known calmodulin binding that facilitates the extension by altering the strain path in myosin VI. Sequence analysis of the proximal tail domain suggests that further calmodulin binding sites open up when the domain's three-helix bundle is unfolded and that subsequent calmodulin binding stabilizes the extended lever arms.

Ferroelectric polymer-based artificial synapse for neuromorphic computing.

Recently, various efforts have been made to implement synaptic characteristics with a ferroelectric field-effect transistor (FeFET), but in-depth physical analyses have not been reported thus far. Here, we investigated the effects by (i) the formation temperature of the ferroelectric material, poly(vinylidene fluoride-trifluoroethylene) P(VDF-TrFE) and (ii) the nature of the contact metals (Ti, Cr, Pd) of the FeFET on the operating performance of a FeFET-based artificial synapse in terms of various synaptic performance indices. Excellent ferroelectric properties were induced by maximizing the size and coverage ratio of the ß-phase domains by annealing the P(VDF-TrFE) film at 140 °C. A metal that forms a relatively high barrier improved the dynamic range and nonlinearity by suppressing the contribution of the tunneling current to the post-synaptic current. Subsequently, we studied the influence of the synaptic characteristics on the training and recognition tasks by using two MNIST datasets (fashion and handwritten digits) and the multi-layer perceptron concept of neural networks.

Immuno-enhancement effects of Korean Red Ginseng in healthy adults: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Most clinical studies of immune responses activated by Korean Red Ginseng (KRG) have been conducted exclusively in patients. However, there is still a lack of clinical research on immune-boosting benefits of KRG for healthy persons. This study aims to confirm how KRG boosts the immune system of healthy subjects. METHODS: A total of 100 healthy adult subjects were randomly divided into two groups that took either a 2 g KRG tablet or a placebo per day for 8 weeks. The primary efficacy evaluation variables included changes in T cells, B cells, and white blood cells (WBCs) before and after eight weeks of KRG ingestion. Cytokines (TNF-α, INF-γ, IL-2 and IL-4), WBC differential count, and incidence of colds were measured in the secondary efficacy evaluation variables. Safety evaluation variables were used to identify changes in laboratory test results that incorporated adverse reactions, vital signs, hematological tests, blood chemistry tests, and urinalysis. RESULTS: Compared to the placebo group, the KRG intake group showed a significant increase in the number of T cells (CD3) and its subtypes (CD4 and CD8), B cells, and the WBC count before and after eight weeks of the intake. There were no clinically significant adverse reactions or other notable results in the safety evaluation factors observed. CONCLUSION: This study has proven through its eight-week intake test and subsequent analysis that KRG boosts the immune system through an increase in T cells, B cells, and WBCs, and that it is safe according to the study's safety evaluation.