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A circadian clock is reconstituted in vitro by incubating three proteins, KaiA, KaiB, and KaiC from the non-nitrogen-fixing cyanobacterium Synechococcus elongatus PCC 7942 in the presence of ATP. Leptolyngbya boryana is a filamentous cyanobacterium that grows diazotrophically under microoxic conditions. Among the aforementioned proteins, KaiC is the main clock oscillator belonging to the RecA ATPase superfamily. Genomic studies have revealed the presence of many genes encoding KaiC family ATPases in archaea and bacteria; however, very few have been analyzed in detail. For example, the L. boryana genome encodes two kaiC homologs designated as LbkaiC1 (LBWT_14830) and LbkaiC2 (LBWT_17950). LbKaiC1 is highly similar to KaiC from S. elongatus PCC 7942 compared with LbKaiC2. LbKaiC1 and LbKaiC2 were purified as Strep-tag fusion proteins. LbKaiC1 formed a hexamer and exhibited autophosphorylation, autodephosphorylation, and ATPase activities. Furthermore, it exhibited circadian phosphorylation rhythm in the presence of KaiA and KaiB from S. elongatus PCC 7942, indicating that LbKaiC1 is the central oscillator of the circadian clock in L. boryana. The temporal separation of nitrogen fixation from photosynthesis may be supported by the circadian rhythm generated by LbKaiC1 in L. boryana. LbKaiC2 had low ATPase activity, which depended on temperature, and its autophosphorylation activity was not detected like a circadian oscillator KaiC. Although the function of LbKaiC2 remains unknown, this work will provide comprehensive understanding of KaiC family ATPases., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The early and highly accurate prediction of COVID-19 based on medical images can speed up the diagnostic process and thereby mitigate disease spread; therefore, developing AI-based models is an inevitable endeavor. The presented work, to our knowledge, is the first to expand the model space and identify a better performing model among 10,000 constructed deep transfer learning (DTL) models as follows. First, we downloaded and processed 4481 CT and X-ray images pertaining to COVID-19 and non-COVID-19 patients, obtained from the Kaggle repository. Second, we provide processed images as inputs to four pre-trained deep learning models (ConvNeXt, EfficientNetV2, DenseNet121, and ResNet34) on more than a million images from the ImageNet database, in which we froze the convolutional and pooling layers pertaining to the feature extraction part while unfreezing and training the densely connected classifier with the Adam optimizer. Third, we generate and take a majority vote of two, three, and four combinations from the four DTL models, resulting in [Formula: see text] DTL models. Then, we combine the 11 DTL models, followed by consecutively generating and taking the majority vote of [Formula: see text] DTL models. Finally, we select [Formula: see text] DTL models from [Formula: see text] Experimental results from the whole datasets using five-fold cross-validation demonstrate that the best generated DTL model, named HC, achieving the best AUC of 0.909 when applied to the CT dataset, while ConvNeXt yielded a higher marginal AUC of 0.933 compared to 0.93 for HX when considering the X-ray dataset. These promising results set the foundation for promoting the large generation of models (LGM) in AI., (© 2024. The Author(s).)

An earthquake with a moment magnitude of 7.5 (Mw) struck the northern Noto Peninsula, Ishikawa Prefecture, Japan, at 16:10 local time on January 1, 2024. This earthquake triggered a tsunami that propagated along the coastline of Ishikawa, Toyama, and Niigata Prefectures facing the Sea of Japan and significantly damaged coastal communities and infrastructure. Approximately 70 researchers from 23 universities or other institutes throughout Japan formed a joint research group to conduct a post-tsunami survey along a 340 km stretch of the coast. Based on the watermarks and traces of the tsunami, the inundation and run-up heights were surveyed using total stations, automatic optical levels, laser range finders, and a real-time kinematic (RTK) Global Navigation Satellite System (GNSS). The tidal correction was adjusted using astronomical tidal tables. In total, 303 survey records have been compiled, generating the NP2024TS (Noto Peninsula 2024 Tsunami Survey) dataset. This dataset provides comprehensive information on the inundation and run-up heights of the tsunami, which is useful for understanding tsunami characteristics and validating numerical tsunami models., (© 2024. The Author(s).)

Pupil contagion refers to the observer's pupil-diameter changes in response to changes in the pupil diameter of others. Recent studies on the other-race effect on pupil contagion have mainly focused on using eye region images as stimuli, revealing the effect in adults but not in infants. To address this research gap, the current study used whole-face images as stimuli to assess the pupil-diameter response of 5-6-month-old and 7-8-month-old infants to changes in the pupil-diameter of both upright and inverted unfamiliar-race faces. The study initially hypothesized that there would be no pupil contagion in either upright or inverted unfamiliar-race faces, based on our previous finding of pupil contagion occurring only in familiar-race faces among 5-6-month-old infants. Notably, the current results indicated that 5-6-month-old infants exhibited pupil contagion in both upright and inverted unfamiliar-race faces, while 7-8-month-old infants showed this effect only in upright unfamiliar-race faces. These results demonstrate that the face inversion effect of pupil contagion does not occur in 5-6-month-old infants, thereby suggesting the presence of the other-race effect in pupil contagion among this age group. Overall, this study provides the first evidence of the other-race effect on infants' pupil contagion using face stimuli., (© 2024. The Author(s).)

The addition of surface acoustic wave (SAW) technologies to microfluidics has greatly advanced lab-on-a-chip applications due to their unique and powerful attributes, including high-precision manipulation, versatility, integrability, biocompatibility, contactless nature, and rapid actuation. However, the development of SAW microfluidic devices is limited by complex and time-consuming micro/nanofabrication techniques and access to cleanroom facilities for multistep photolithography and vacuum-based processing. To simplify the fabrication of SAW microfluidic devices with customizable dimensions and functions, we utilized the additive manufacturing technique of aerosol jet printing. We successfully fabricated customized SAW microfluidic devices of varying materials, including silver nanowires, graphene, and poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS). To characterize and compare the acoustic actuation performance of these aerosol jet printed SAW microfluidic devices with their cleanroom-fabricated counterparts, the wave displacements and resonant frequencies of the different fabricated devices were directly measured through scanning laser Doppler vibrometry. Finally, to exhibit the capability of the aerosol jet printed devices for lab-on-a-chip applications, we successfully conducted acoustic streaming and particle concentration experiments. Overall, we demonstrated a novel solution-based, direct-write, single-step, cleanroom-free additive manufacturing technique to rapidly develop SAW microfluidic devices that shows viability for applications in the fields of biology, chemistry, engineering, and medicine., Competing Interests: Competing interestsT.J.H. has co-founded a start-up company, Ascent Bio-Nano Technologies Inc., to commercialize technologies involving acoustofluidics and acoustic tweezers., (© The Author(s) 2024.)

We introduce a three-dimensional mathematical model for the dynamics of vascular endothelial cells during sprouting angiogenesis. Angiogenesis is the biological process by which new blood vessels form from existing ones. It has been the subject of numerous theoretical models. These models have successfully replicated various aspects of angiogenesis. Recent studies using particle-based models have highlighted the significant influence of cell shape on network formation, with elongated cells contributing to the formation of branching structures. While most mathematical models are two-dimensional, we aim to investigate whether ellipsoids also form branch-like structures and how their shape affects the pattern. In our model, the shape of a vascular endothelial cell is represented as a spheroid, and a discrete dynamical system is constructed based on the simple assumption of two-body interactions. Numerical simulations demonstrate that our model reproduces the patterns of elongation and branching observed in the early stages of angiogenesis. We show that the pattern formation of the cell population is strongly dependent on the cell shape. Finally, we demonstrate that our current mathematical model reproduces the cell behaviours, specifically cell-mixing, observed in sprouts., (© 2023. The Author(s).)

Biennial Update Reports (BURs) are essential requirements from the United Nations Framework Convention on Climate Change (UNFCCC). However, many non-Annex I countries have not submitted these reports due to difficulties in compiling the inventories. We developed a satellite-based method for the top-down inverse estimation of CO 2 emissions using partial-column data in the lower troposphere obtained by the Greenhouse Gases Observing Satellite, adopted to validate the Mongolian 2 nd BUR (BUR2) for the energy sector in 2018. The estimated CO 2 emissions were only 1.5% higher than those reported in the BUR2; these were also very close (4.2% smaller) to estimates from the Emission Database for Global Atmospheric Research. Mongolia is the first country to introduce an independent inverse estimate in its BUR, thereby increasing scientific transparency. Our method could be applied into other countries and could be incorporated into UNFCCC reporting guidelines, significantly improving global CO 2 emission estimates., (© 2023. Springer Nature Limited.)

Human infants cannot report their experiences, limiting what we can learn about their bodily awareness. However, visual cortical responses to the body, linked to visual awareness and selective attention in adults, can be easily measured in infants and provide a promising marker of bodily awareness in early life. We presented 4- and 8-month-old infants with a flickering (7.5 Hz) video of a hand being stroked and recorded steady-state visual evoked potentials (SSVEPs). In half of the trials, the infants also received tactile stroking synchronously with visual stroking. The 8-month-old, but not the 4-month-old infants, showed a significant enhancement of SSVEP responses when they received tactile stimulation concurrent with the visually observed stroking. Follow-up experiments showed that this enhancement did not occur when the visual hand was presented in an incompatible posture with the infant's own body or when the visual stimulus was a body-irrelevant video. Our findings provide a novel insight into the development of bodily self-awareness in the first year of life., (© 2023. Springer Nature Limited.)

The centre of the Milky Way Galaxy hosts a black hole with a solar mass of about 4 million (Sagittarius A * (Sgr A)) that is very quiescent at present with a luminosity many orders of magnitude below those of active galactic nuclei 1 . Reflection of X-rays from Sgr A * by dense gas in the Galactic Centre region offers a means to study its past flaring activity on timescales of hundreds and thousands of years 2 . The shape of the X-ray continuum and the strong fluorescent iron line observed from giant molecular clouds in the vicinity of Sgr A * are consistent with the reflection scenario 3-5 . If this interpretation is correct, the reflected continuum emission should be polarized 6 . Here we report observations of polarized X-ray emission in the direction of the molecular clouds in the Galactic Centre using the Imaging X-ray Polarimetry Explorer. We measure a polarization degree of 31% ± 11%, and a polarization angle of -48° ± 11°. The polarization angle is consistent with Sgr A * being the primary source of the emission, and the polarization degree implies that some 200 years ago, the X-ray luminosity of Sgr A * was briefly comparable to that of a Seyfert galaxy., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Veterinary medicine has made tremendous progress for domestic dogs, which are irreplaceable family members enriching human life. Nevertheless, no adequate supply system exists for their blood products. This study examined the synthesis, structure, safety, and efficacy of poly(2-ethyl-2-oxazoline)-conjugated porcine serum albumin (POx-PSA) as an artificial plasma expander for dogs. The aqueous POx-PSA solution showed moderately high colloid osmotic pressure and good blood cell compatibility. Actually, lyophilized powder stored for 1 year can regenerate into a homogeneous solution. The circulation half-life of POx-PSA in rats was 2.1-fold longer than that of naked PSA. Rats produced neither anti-PSA IgG antibody nor anti-POx IgG antibody, which suggests excellent immunological stealth properties of POx-PSA. Complete resuscitation of hemorrhagic shock in rats was achieved soon after injection of POx-PSA solution. Serum biochemistry tests and histopathological observations indicated no abnormality in the related organs. When POx-PSA was administered to dogs intravenously, (i) no serum biochemical or hematological alteration was observed, also (ii) no overt deterioration of animal health was observed. These results indicate that POx-PSA has potential as an artificial plasma expander for dogs., (© 2023. The Author(s).)

In soccer game analysis, the widespread availability of play-by-play and tracking data has made it possible to test mathematical models that have been discussed mainly theoretically. One of the essential models in soccer game analysis is a motion model that predicts the arrival point of a player in t s. Although many space evaluation and pass prediction methods rely on motion models, the validity of each has not been fully clarified. This study focuses on the motion model proposed by Fujimura and Sugihara (Fujimura-Sugihara model) under sprint conditions based on the equation of motion. A previous study indicated that the Fujimura-Sugihara model is ineffective for soccer games because it generates a circular arrival region. This study aims to examine the validity of the Fujimura-Sugihara model using soccer tracking data. Specifically, we quantitatively compare the arrival regions of players between the model and real data. We show that the boundary of the player's arrival region is circular rather than elliptical, which is consistent with the model. We also show that the initial speed dependence of the arrival region satisfies the solution of the model. Furthermore, we propose a method for estimating valid kinetic parameters in the model directly from tracking data and discuss the limitations of the model for soccer games based on the estimated parameters., (© 2023. The Author(s).)

The integrated analysis of multiple gene expression profiles previously measured in distinct studies is problematic since missing both sample matches and common labels prevent their integration in fully data-driven, unsupervised training. In this study, we propose a strategy to enable the integration of multiple gene expression profiles among multiple independent studies with neither labeling nor sample matching using tensor decomposition unsupervised feature extraction. We apply this strategy to Alzheimer's disease (AD)-related gene expression profiles that lack precise correspondence among samples, including AD single-cell RNA sequence (scRNA-seq) data. We were able to select biologically reasonable genes using the integrated analysis. Overall, integrated gene expression profiles can function analogously to prior- and/or transfer-learning strategies in other machine-learning applications. For scRNA-seq, the proposed approach significantly reduces the required computational memory., (© 2022. The Author(s).)

Pulsar wind nebulae are formed when outflows of relativistic electrons and positrons hit the surrounding supernova remnant or interstellar medium at a shock front. The Vela pulsar wind nebula is powered by a young pulsar (B0833-45, aged 11,000 years) 1 and located inside an extended structure called Vela X, which is itself inside the supernova remnant 2 . Previous X-ray observations revealed two prominent arcs that are bisected by a jet and counter jet 3,4 . Radio maps have shown high linear polarization of 60% in the outer regions of the nebula 5 . Here we report an X-ray observation of the inner part of the nebula, where polarization can exceed 60% at the leading edge-approaching the theoretical limit of what can be produced by synchrotron emission. We infer that, in contrast with the case of the supernova remnant, the electrons in the pulsar wind nebula are accelerated with little or no turbulence in a highly uniform magnetic field., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Although small organic molecules in cells have been considered important to control the functions of proteins, their electronic fluctuation and the intermolecular interaction, which is physicochemical origin of the molecular functions, under physiological conditions, i.e., dilute aqueous solutions (0.18 mol L -1 ), has never been clarified due to the lack of observation methods with both accuracy and efficiency. Herein, the time evolutions of the interactions in dilute aqueous trimethylamine N-oxide (TMAO) and tert-butyl alcohol (TBA) solutions were analyzed via ab initio molecular dynamics simulations accelerated with the fragment molecular theory. It has been known that TMAO and TBA have similar structures, but opposite physiological functions to stabilize and destabilize proteins. It was clarified that TMAO induced stable polarization and charge-transfer interactions with water molecules near the hydrophilic group, and water molecules were caught even near the CH 3 - group. Those should affect protein stabilization. Understanding the solution dynamics will contribute to artificial chaperone design in next generation medicine., (© 2022. The Author(s).)

Many genes responsible for Malignant mesothelioma (MM) have been identified as tumor suppressor genes and it is difficult to target these genes directly at a molecular level. We searched for the gene which showed synthetic lethal phenotype with LATS2, one of the MM causative genes and one of the kinases in the Hippo pathway. Here we showed that knockdown of SMG6 results in synthetic lethality in LATS2-inactivated cells. We found that this synthetic lethality required the nuclear translocation of YAP1 and TAZ. Both are downstream factors of the Hippo pathway. We also demonstrated that this synthetic lethality did not require SMG6 in nonsense-mediated mRNA decay (NMD) but in regulating telomerase reverse transcriptase (TERT) activity. In addition, the RNA-dependent DNA polymerase (RdDP) activity of TERT was required for this synthetic lethal phenotype. We confirmed the inhibitory effects of LATS2 and SMG6 on cell proliferation in vivo. The result suggests an interaction between the Hippo and TERT signaling pathways. We also propose that SMG6 and TERT are novel molecular target candidates for LATS2-inactivated cancers such as MM., (© 2022. The Author(s).)

Most of the light from blazars, active galactic nuclei with jets of magnetized plasma that point nearly along the line of sight, is produced by high-energy particles, up to around 1 TeV. Although the jets are known to be ultimately powered by a supermassive black hole, how the particles are accelerated to such high energies has been an unanswered question. The process must be related to the magnetic field, which can be probed by observations of the polarization of light from the jets. Measurements of the radio to optical polarization-the only range available until now-probe extended regions of the jet containing particles that left the acceleration site days to years earlier 1-3 , and hence do not directly explore the acceleration mechanism, as could X-ray measurements. Here we report the detection of X-ray polarization from the blazar Markarian 501 (Mrk 501). We measure an X-ray linear polarization degree Π X of around 10%, which is a factor of around 2 higher than the value at optical wavelengths, with a polarization angle parallel to the radio jet. This points to a shock front as the source of particle acceleration and also implies that the plasma becomes increasingly turbulent with distance from the shock., (© 2022. The Author(s).)

Tensor decomposition- and principal component analysis-based unsupervised feature extraction were proposed almost 5 and 10 years ago, respectively; although these methods have been successfully applied to a wide range of genome analyses, including drug repositioning, biomarker identification, and disease-causing genes' identification, some fundamental problems have been identified: the number of genes identified was too small to assume that there were no false negatives, and the histogram of P values derived was not fully coincident with the null hypothesis that principal component and singular value vectors follow the Gaussian distribution. Optimizing the standard deviation such that the histogram of P values is as much as possible coincident with the null hypothesis results in an increase in the number and biological reliability of the selected genes. Our contribution was that we improved these methods so as to be able to select biologically more reasonable differentially expressed genes than the state of art methods that must empirically assume negative binomial distributions and dispersion relation, which is required for the selecting more expressed genes than less expressed ones, which can be achieved by the proposed methods that do not have to assume these., (© 2022. The Author(s).)

This article reports the development of highly waterborne silicon quantum dots (Si QDs) terminated with a reactive group for grafting of biomolecules. Hydrogen-terminated QDs were prepared by thermal disproportionation of amorphous hydrogen silsesquioxane derived from triethoxysilane followed by hydrofluoric etching. Next, the hydrogenated Si surfaces were exposed to 10-undecenoic acid at different temperatures in Ar atmosphere, yielding the termination of the QDs with a carboxyl group. The thermal hydrosilylation of 10-undecenoic acid yielded the termination of the QDs with a carboxyl group. An increase in molecular coverage of an undecanoic acid (UA) monolayer resulted in both the enhanced increase of zeta-potential in a negative direction for a greater water-dispersity and the increase of absolute quantum yield (QY) of photoluminescence (PL). PLQY improved for ~ 1% to 26% with increasing UA coverage. We assessed the molecular interaction between the UA-SiQDs and HeLa cells by means of cellular uptake experiments using the QDs with different UA coverages. Results showed that the QDs with the highest dispersity in water were not internalized in the cells under confocal fluorescence microscopic observation. In contrast, the QDs with lower coverage of UA monolayer were internalized by endocytosis when incubated with HeLa cells. This contrasting observation opens the possibility of successfully preparing carboxy-capped SiQDs that do not allow cellular uptake but are targeted to specific cells by appropriate conjugation with biomolecules., (© 2022. The Author(s).)

Understanding of pollination systems is an important topic for evolutionary ecology, food production, and biodiversity conservation. However, it is difficult to grasp the whole picture of an individual system, because the activity of pollinators fluctuates depending on the flowering period and time of day. In order to reveal effective pollinator taxa and timing of visitation to the reproductive success of plants under the complex biological interactions and fluctuating abiotic factors, we developed an automatic system to take photographs at 5-s intervals to get near-complete flower visitation by pollinators during the entire flowering period of selected flowers of Nelumbo nucifera and track the reproductive success of the same flowers until fruiting. Bee visits during the early morning hours of 05:00-07:59 on the second day of flowering under optimal temperatures with no rainfall or strong winds contributed strongly to seed set, with possible indirect negative effects by predators of the pollinators. Our results indicate the availability of periodic and consecutive photography system in clarifying the plant-pollinator interaction and its consequence to reproductive success of the plant. Further development is required to build a monitoring system to collect higher-resolution time-lapse images and automatically identify visiting insect species in the natural environment., (© 2022. The Author(s).)

Climate change may disrupt species-species interactions via phenological changes in one or both species. To predict and evaluate the influence of climate change on these interactions, long-term monitoring and sampling over large spatial areas are required; however, funding and labor constraints limit data collection. In this study, we predict and evaluate the plant-insect interactions with limited data sets. We examined plant-insect interaction using observational data for development of the crop plant rice (Oryza sativa) and an effective accumulated temperature (EAT) model of two mirid bugs (Stenotus rubrovittatus and Trigonotylus caelestialium). We combined 11 years of records monitoring rice phenology and the predicted phenology of mirid bugs using spatially-explicit EAT models based on both spatially and temporally high resolutions temperature data sets, then evaluated their accuracy using actual pest damage records. Our results showed that the predicted interactions between rice and mirid bugs explained rice damage to some degree. Our approach may apply predicting changes to plant-insect interactions under climate change. As such, combining plant monitoring records and theoretical predictions of insect phenology may be effective for predicting species-species interactions when available data are limited., (© 2022. The Author(s).)

The aim of this randomized controlled trial was to determine the efficacy of stylet angulation at the holding position during tracheal intubation with a McGRATH MAC videolaryngoscope. Patients were randomized to a group for intubation without stylet angulation at the holding position (non-angulation group) and to a group for intubation with stylet angulation at the holding position (angulation group). The primary outcome was the time for placement of the tracheal tube. Sixty patients were analyzed. The mean (standard deviation) times for tube placement were 21.3 (5.6) s in the non-angulation group and 16.9 (3.8) s in the angulation group (P < 0.001). The scores of operator's perception of difficulty in tube delivery, number of attempts for tube delivery, and degrees of extension, abduction, internal rotation of the right upper arm and extension of the right wrist during tube placement in the angulation group were significantly smaller than those in the non-angulation group (P < 0.001, P = 0.002, P < 0.001, P < 0.001, P < 0.001, P < 0.001, respectively). Our results suggest that stylet angulation at the holding position improves maneuverability of the tracheal tube and enables easy, smooth, and swift tube placement during tracheal intubation with a McGRATH MAC videolaryngoscope., (© 2021. The Author(s).)

The amount of carbon stored in deadwood is equivalent to about 8 per cent of the global forest carbon stocks 1 . The decomposition of deadwood is largely governed by climate 2-5 with decomposer groups-such as microorganisms and insects-contributing to variations in the decomposition rates 2,6,7 . At the global scale, the contribution of insects to the decomposition of deadwood and carbon release remains poorly understood 7 . Here we present a field experiment of wood decomposition across 55 forest sites and 6 continents. We find that the deadwood decomposition rates increase with temperature, and the strongest temperature effect is found at high precipitation levels. Precipitation affects the decomposition rates negatively at low temperatures and positively at high temperatures. As a net effect-including the direct consumption by insects and indirect effects through interactions with microorganisms-insects accelerate the decomposition in tropical forests (3.9% median mass loss per year). In temperate and boreal forests, we find weak positive and negative effects with a median mass loss of 0.9 per cent and -0.1 per cent per year, respectively. Furthermore, we apply the experimentally derived decomposition function to a global map of deadwood carbon synthesized from empirical and remote-sensing data, obtaining an estimate of 10.9 ± 3.2 petagram of carbon per year released from deadwood globally, with 93 per cent originating from tropical forests. Globally, the net effect of insects may account for 29 per cent of the carbon flux from deadwood, which suggests a functional importance of insects in the decomposition of deadwood and the carbon cycle., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Coronavirus disease 2019 (COVID-19) is raging worldwide. This potentially fatal infectious disease is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the complete mechanism of COVID-19 is not well understood. Therefore, we analyzed gene expression profiles of COVID-19 patients to identify disease-related genes through an innovative machine learning method that enables a data-driven strategy for gene selection from a data set with a small number of samples and many candidates. Principal-component-analysis-based unsupervised feature extraction (PCAUFE) was applied to the RNA expression profiles of 16 COVID-19 patients and 18 healthy control subjects. The results identified 123 genes as critical for COVID-19 progression from 60,683 candidate probes, including immune-related genes. The 123 genes were enriched in binding sites for transcription factors NFKB1 and RELA, which are involved in various biological phenomena such as immune response and cell survival: the primary mediator of canonical nuclear factor-kappa B (NF-κB) activity is the heterodimer RelA-p50. The genes were also enriched in histone modification H3K36me3, and they largely overlapped the target genes of NFKB1 and RELA. We found that the overlapping genes were downregulated in COVID-19 patients. These results suggest that canonical NF-κB activity was suppressed by H3K36me3 in COVID-19 patient blood., (© 2021. The Author(s).)

The skin barrier is provided by the organized multi-layer structure of epidermal cells, which is dynamically maintained by a continuous supply of cells from the basal layer. The epidermal homeostasis can be disrupted by various skin diseases, which often cause morphological changes not only in the epidermis but in the dermis. We present a three-dimensional agent-based computational model of the epidermis that takes into account the deformability of the dermis. Our model can produce a stable epidermal structure with well-organized layers. We show that its stability depends on the cell supply rate from the basal layer. Modeling the morphological change of the dermis also enables us to investigate how the stiffness of the dermis affects the structure and barrier functions of the epidermis. Besides, we show that our model can simulate the formation of a corn (clavus) by assuming hyperproliferation and rapid differentiation. We also provide experimental data for human corn, which supports the model assumptions and the simulation result.

The effect of interactions between perfluorooctanesulfonic (PFOS)/perfluorooctanoic acid (PFOA) levels and nuclear receptor genotypes on fatty acid (FA) levels, including those of triglycerides, is not clear understood. Therefore, in the present study, we aimed to analyse the association of PFOS/PFOA levels and single-nucleotide polymorphisms (SNPs) in nuclear receptors with FA levels in pregnant women. We analysed 504 mothers in a birth cohort between 2002 and 2005 in Japan. Serum PFOS/PFOA and FA levels were measured using liquid chromatography-tandem mass spectrometry and gas chromatography-mass spectrometry. Maternal genotypes in PPARA (rs1800234; rs135561), PPARG (rs3856806), PPARGC1A (rs2970847; rs8192678), PPARD (rs1053049; rs2267668), CAR (rs2307424; rs2501873), LXRA (rs2279238) and LXRB (rs1405655; rs2303044; rs4802703) were analysed. When gene-environment interaction was considered, PFOS exposure (log 10 scale) decreased palmitic, palmitoleic, and oleic acid levels (log 10 scale), with the observed β in the range of - 0.452 to - 0.244; PPARGC1A (rs8192678) and PPARD (rs1053049; rs2267668) genotypes decreased triglyceride, palmitic, palmitoleic, and oleic acid levels, with the observed β in the range of - 0.266 to - 0.176. Interactions between PFOS exposure and SNPs were significant for palmitic acid (P int  = 0.004 to 0.017). In conclusion, the interactions between maternal PFOS levels and PPARGC1A or PPARD may modify maternal FA levels.

Droplet microfluidics has emerged as a powerful technology for improving the culturing efficiency of environmental microorganisms. However, its widespread adoption has been limited due to considerable technical challenges, especially related to identification and manipulation of individual growth-positive droplets. Here, we combined microfluidic droplet technology with on-chip "fluorescent nucleic acid probe in droplets for bacterial sorting" (FNAP-sort) for recovery of growth-positive droplets and droplet microdispensing to establish an end-to-end workflow for isolation and culturing of environmental microbes. As a proof-of-concept, we demonstrate the ability of our technique to yield high-purity cultures of rare microorganisms from a representative complex environmental microbiome. As our system employs off-the-shelf commercially available equipment, we believe that it can be readily adopted by others and may thus find widespread use toward culturing the high proportion of as-of-yet uncultured microorganisms in different biomes.

Topological defects in liquid crystals (LCs) dominate molecular alignment/motion in many cases. Here, the neural network (NN) function has been introduced to predict the LC orientation condition (orientation angle and order parameter) at local positions around topological defects from the phase/polarization microscopic color images. The NN function was trained in advance by using the color information of an LC in a planar alignment cell for different orientation angles and temperatures. The photo-induced changes of LC molecules around topological defects observed by the time-resolved measurement was converted into the image sequences of the orientation angle and the order parameter change. We found that each pair of brushes with different colors around topological defects showed different orientation angle and ordering changes. The photo-induced change was triggered by the photoisomerization reaction of molecules, and one pair of brushes increased in its order parameter just after light irradiation, causing gradual rotation in the brush. The molecules in the other pair of brushes were disordered and rotated by the effect of the initially affected region. This combination approach of the time-resolved phase/polarization microscopy and the NN function can provide detailed information on the molecular alignment dynamics around the topological defects.

Although hypoxia is a critical factor that can drive the progression of various diseases, the mechanism underlying hypoxia itself remains unclear. Recently, m6A has been proposed as an important factor driving hypoxia. Despite successful analyses, potential genes were not selected with statistical significance but were selected based solely on fold changes. Because the number of genes is large while the number of samples is small, it was impossible to select genes using conventional feature selection methods with statistical significance. In this study, we applied the recently proposed principal component analysis (PCA), tensor decomposition (TD), and kernel tensor decomposition (KTD)-based unsupervised feature extraction (FE) to a hypoxia data set. We found that PCA, TD, and KTD-based unsupervised FE could successfully identify a limited number of genes associated with altered gene expression and m6A profiles, as well as the enrichment of hypoxia-related biological terms, with improved statistical significance.

Recently, the structural analysis of protein complexes by cryo-electron microscopy (cryo-EM) single particle analysis (SPA) has had great impact as a biophysical method. Many results of cryo-EM SPA are based on data acquired on state-of-the-art cryo-electron microscopes customized for SPA. These are currently only available in limited locations around the world, where securing machine time is highly competitive. One potential solution for this time-competitive situation is to reuse existing multi-purpose equipment, although this comes with performance limitations. Here, a multi-purpose TEM with a side entry cryo-holder was used to evaluate the potential of high-resolution SPA, resulting in a 3 Å resolution map of apoferritin with local resolution extending to 2.6 Å. This map clearly showed two positions of an aromatic side chain. Further, examination of optimal imaging conditions depending on two different multi-purpose electron microscope and camera combinations was carried out, demonstrating that higher magnifications are not always necessary or desirable. Since automation is effectively a requirement for large-scale data collection, and augmenting the multi-purpose equipment is possible, we expanded testing by acquiring data with SerialEM using a β-galactosidase test sample. This study demonstrates the possibilities of more widely available and established electron microscopes, and their applications for cryo-EM SPA.

In football game analysis, space evaluation is an important issue because it is directly related to the quality of ball passing or player formations. Previous studies have primarily focused on a field division approach wherein a field is divided into dominant regions in which a certain player can arrive prior to any other players. However, the field division approach is oversimplified because all locations within a region are regarded as uniform herein. The objective of the current study is to propose a fundamental framework for space evaluation based on field weighting. In particular, we employed the motion model and calculated a minimum arrival time [Formula: see text] for each player to all locations on the football field. Our main contribution is that two variables [Formula: see text] and [Formula: see text] corresponding to the minimum arrival time for offense and defense teams are considered; using [Formula: see text] and [Formula: see text], new orthogonal variables [Formula: see text] and [Formula: see text] are defined. In particular, based on real datasets comprising of data from 45 football games of the J1 League in 2018, we provide a detailed characterization of [Formula: see text] and [Formula: see text] in terms of ball passing. By using our method, we found that [Formula: see text] and [Formula: see text] represent the degree of safety for a pass made to [Formula: see text] at t and degree of sparsity of [Formula: see text] at t, respectively; the success probability of passes could be well-fitted using a sigmoid function. Moreover, a new type of field division approach and evaluation of ball passing just before shots using real game data are discussed.

Streptozotocin administration to mice (STZ-mice) induces type I diabetes and hepatocellular carcinoma (HCC). We attempted to elucidate the carcinogenic mechanism and the miRNA expression status in the liver and blood during the precancerous state. Serum and liver tissues were collected from STZ-mice and non-treated mice (CTL-mice) at 6, 10, and 12 W. The exosome enriched fraction extracted from serum was used. Hepatic histological examination and hepatic and exosomal miRNA expression analysis were serially performed using next-generation sequencing (NGS). Human miRNA expression analysis of chronic hepatitis liver tissue and exosomes, which were collected before starting the antiviral treatment, were also performed. No inflammation or fibrosis was found in the liver of CTL-mice during the observation period. In STZ-mice, regeneration and inflammation of hepatocytes was found at 6 W and nodules of atypical hepatocytes were found at 10 and 12 W. In the liver tissue, during 6-12 W, the expression levels of let-7f-5p, miR-143-3p, 148a-3p, 191-5p, 192-5p, 21a-5p, 22-3p, 26a-5p, and 92a-3p was significantly increased in STZ-mice, and anti-oncogenes of their target gene candidates were down-regulated. miR-122-5p was also significantly down-regulated in STZ-mice. Fifteen exosomal miRNAs were upregulated in STZ-mice. Six miRNAs (let-7f-5p, miR-10b-5p, 143-3p, 191-5p, 21a-5p, and 26a-5p) were upregulated, similarly to human HCC cases. From the precancerous state, aberrant expression of hepatic miRNAs has already occurred, and then, it can promote carcinogenesis. In exosomes, the expression pattern of common miRNAs between mice and humans before carcinogenesis was observed and can be expected to be developed as a cancer predictive marker.

Different from typical LexA repressors in heterotrophic bacteria exerting SOS response by auto-cleavage, cyanobacterial LexAs, especially that of Synechocystis sp. PCC 6803 (S.6803), have been suggested be involved in regulation of a number of genes related to various cellular processes, rather than the typical SOS regulon. When and how cyanobacterial LexAs are triggered to regulate its target genes have remained unknown. In this study, we found the profound repressing effect of LexA on salt-stress inducible genes in S.6803. The repressing activity of LexA was likely to persist during salt stress and the salt response of these genes was mainly achieved by other regulators than LexA, suggesting that the physiological role of LexA is fine-tuning of gene expression in response to environmental changes. Although the amount and oligomeric state of LexA were unchanged upon salt stress, two-dimensional electrophoresis and liquid chromatography-tandem mass spectrometry analyses detected a change in posttranslational modification in a small fraction of LexA molecules, possibly dephosphorylation of Ser 173 , after 30 min upon the upshift in salt concentration. Activity of LexA in S.6803 may be under gradual control by posttranslational modification to fine-tune gene expression, which is contrasted with the digital switching-off regulation by auto-cleavage in heterotrophic bacteria.

Cancer is a highly complex disease caused by multiple genetic factors. MicroRNA (miRNA) and mRNA expression profiles are useful for identifying prognostic biomarkers for cancer. Kidney renal clear cell carcinoma (KIRC), which accounts for more than 70% of all renal malignant tumour cases, was selected for our analysis. Traditional methods of identifying cancer prognostic markers may not be accurate. Tensor decomposition (TD) is a useful method uncovering the underlying low-dimensional structures in the tensor. The TD-based unsupervised feature extraction method was applied to analyse mRNA and miRNA expression profiles. Biological annotations of the prognostic miRNAs and mRNAs were examined utilizing the pathway and oncogenic signature databases DIANA-miRPath and MSigDB. TD identified the miRNA signatures and the associated genes. These genes were found to be involved in cancer-related pathways, and 23 genes were significantly correlated with the survival of KIRC patients. We demonstrated that the results are robust and not highly dependent upon the databases we selected. Compared with traditional supervised methods tested, TD achieves much better performance in selecting prognostic miRNAs and mRNAs. These results suggest that integrated analysis using the TD-based unsupervised feature extraction technique is an effective strategy for identifying prognostic signatures in cancer studies.

To monitor and manage biodiversity, surrogate species (i.e., indicator, umbrella and flagship species) have been proposed where conservation resources are focused on a limited number of focal organisms. Using data obtained from 78 sites across six rivers in the mainland Japan and the Amami-Oshima Island, we demonstrate that two anguillids - the Japanese eel (Anguilla japonica) and the giant mottled eel (A. marmorata) - can act as surrogate species for conservation of freshwater biodiversity. Anguillid eels were the widest topographically-distributed species ranging from near the mouth to the upper reaches of rivers. Moreover, stable isotopic analyses indicated that eels are likely one of the highest-order predators in freshwater ecosystems. A significant positive relationship was found between the density of eels and the number of other diadromous species collected. However, the optimal models revealed that both the density of eels and the number of other diadromous species were significantly negatively correlated with distance from the river mouth and cumulative height of trans-river structures from the river mouth to each site. This suggests the positive relationship between eel density and number of other diadromous species was indirect and related to river-ocean connectivity. Given their catadromous life-cycle, and global commercial and cultural importance, as a taxa, anguillid eels can act as indicator, umbrella and flagship species, and a comprehensive surrogate for conservation of freshwater biodiversity.

Typhoons and associated storm waves in the northwestern Pacific Ocean commonly cause coastal disasters. The possibility remains that an even stronger typhoon than the strongest one observed to date might have occurred before. The development of a method to estimate a maximum intensity of past typhoons over thousands of years is important for paleoclimatology, paleoceanography and disaster prevention. Numerous storm wave boulders exist on reefs in the Ryukyu Islands, Japan, which have been deposited to their present position by the cumulative effects of the past storm waves. These boulders can be used as proxies for the hydrodynamic conditions of the largest waves from past events. Here, we present numerical computations for storm waves and boulder transport with the boulder distribution as a constraint factor to estimate the maximum intensities of storm waves and their causative typhoon events over the past 3500 years. Though the intensities of the maximum estimated waves and associated typhoon events were slightly stronger than those recorded over the past ~70 years in the Ryukyu Islands, our results suggest that no abnormally intense typhoon has struck the Ryukyu Islands in the past 3500 years. The potential impact from tsunamis remains uncertain; however, our results are meteorologically reasonable.

Nucleos(t)ide analog (NA) therapy has proven effective in treating chronic hepatitis B. However, NAs frequently result in viral relapse after the cessation of therapy. This is because NAs cannot fully eliminate the viral episomal covalently closed circular DNA (cccDNA) in the nucleus. In this study, we identified small molecular compounds that control host factors related to viral replication using in silico screening with simulated annealing based on bioinformatics for protein-ligand flexible docking. Twelve chemical compound candidates for alpha-glucosidase (AG) inhibitors were identified from a library of chemical compounds and used to treat fresh human hepatocytes infected with HBV. They were then monitored for their anti-viral effects. HBV replication was inhibited by one candidate (1-[3-(4-tert-butylcyclohexyl)oxy-2-hydroxypropyl]-2,2,6,6-tetramethylpiperidin-4-ol) in a dose-dependent manner. This compound significantly reduced ccc DNA production, compared to Entecavir (p < 0.05), and had a lower anti-AG effect. Gene expression analysis and structural analysis of this compound showed that its inhibitive effect on HBV was via interaction with Sp1. The nuclear transcription factor Sp1 acts on multiple regions of HBV to suppress HBV replication. Identifying candidates that control nuclear transcription factors facilitate the development of novel therapies. Drugs with a mechanism different from NA are promising for the elimination of HBV.

Potential inhibitors of a target biomolecule, NAD-dependent deacetylase Sirtuin 1, were identified by a contest-based approach, in which participants were asked to propose a prioritized list of 400 compounds from a designated compound library containing 2.5 million compounds using in silico methods and scoring. Our aim was to identify target enzyme inhibitors and to benchmark computer-aided drug discovery methods under the same experimental conditions. Collecting compound lists derived from various methods is advantageous for aggregating compounds with structurally diversified properties compared with the use of a single method. The inhibitory action on Sirtuin 1 of approximately half of the proposed compounds was experimentally accessed. Ultimately, seven structurally diverse compounds were identified.

Alzheimer disease (AD) is a devastating neurological disorder, which initiates from hippocampus and proliferates to cortical regions. The neurons of hippocampus require higher energy to preserve the firing pattern. In AD, aberrant energy metabolism is the critical factor for neurodegeneration. However, the reason for the energy crisis in hippocampus neurons is still unresolved. Transcriptome analysis enables us in understanding the underlying mechanism of energy crisis. In this study, we identified variants/differential gene/transcript expression profiles from hippocampus RNA-seq data. We predicted the effect of variants in transcription factor (TF) binding using in silico tools. Further, a hippocampus-specific co-expression and functional interaction network were designed to decipher the relationships between TF and differentially expressed genes (DG). Identified variants predominantly influence TF binding, which subsequently regulates the DG. From the results, we hypothesize that the loss of vascular integrity is the fundamental attribute for the energy crisis, which leads to neurodegeneration.

A core symptom of autism spectrum disorder (ASD) is restricted and repetitive behavior, characterized partly by insistence on sameness and excessively focused interest. This behavior has often been interpreted as a manifestation of anxiety and fear triggered by resistance to change. The implicit assumption underlying this interpretation is that perception per se (such as the judgment of sameness and changes in sensory stimuli) is not different between ASD and typically developed (TD) individuals, but that only the emotional response to the same amount of perceived change is. However, few studies have examined how individuals with ASD actually perceive a repeated presentation of the same sensory stimulus. To explore this issue, we conducted a listening test to compare perception of a repeated sound pattern, namely a spoken word, between ASD and TD groups. Prolonged listening to a repeated word without a pause may induce perceptual changes, which is known as the verbal transformation effect. We discovered that individuals with ASD tend to perceive more drastic changes or differences for the same repeated auditory pattern. This suggests that such variable perception incites individuals with ASD to persist for sameness.

Sound symbolism, which is the systematic and non-arbitrary link between a word and its meaning, has been suggested to bootstrap language acquisition in infants. However, it is unclear how sound symbolism is processed in the infants' brain. To address this issue, we investigated the cortical response in 11-month-old infants in relation to sound-symbolic correspondences using near-infrared spectroscopy (NIRS). Two types of stimuli were presented: a novel visual stimulus (e.g., a round shape) followed by a novel auditory stimulus that either sound-symbolically matched (moma) or mismatched (kipi) the shape. We found a significant hemodynamic increase in the right temporal area, when the sound and the referent sound were symbolically matched, but this effect was limited to the moma stimulus. The anatomical locus corresponds to the right posterior superior temporal sulcus (rSTS), which is thought to process sound symbolism in adults. These findings suggest that prelinguistic infants have the biological basis to detect cross-modal correspondences between word sounds and visual referents.

In competitive team sports, players maintain a certain formation during a game to achieve effective attacks and defenses. For the quantitative game analysis and assessment of team styles, we need a general framework that can characterize such formation structures dynamically. This paper develops a clustering algorithm for formations of multiple football (soccer) games based on the Delaunay method, which defines the formation of a team as an adjacency matrix of Delaunay triangulation. We first show that heat maps of entire football games can be clustered into several average formations: "442", "4141", "433", "541", and "343". Then, using hierarchical clustering, each average formation is further divided into more specific patterns (clusters) in which the configurations of players are different. Our method enables the visualization, quantitative comparison, and time-series analysis for formations in different time scales by focusing on transitions between clusters at each hierarchy. In particular, we can extract team styles from multiple games regarding the positional exchange of players within the formations. Applying our algorithm to the datasets comprising football games, we extract typical transition patterns of the formation for a particular team.

Yawning is contagious in human adults. While infants do not show contagious yawning, it remains unclear whether infants perceive yawning in the same manner as other facial expressions of emotion. We addressed this problem using functional near-infrared spectroscopy (fNIRS) and behavioural experiments. We confirmed behaviourally that infants could discriminate between yawning and unfamiliar mouth movements. Furthermore, we found that the hemodynamic response of infants to a yawning movement was greater than that to mouth movement, similarly to the observations in adult fMRI study. These results suggest that the neural mechanisms underlying yawning movement perception have developed in advance of the development of contagious yawning.

Autism spectrum disorder (ASD) presents certain hallmark features associated with cognitive and social functions, however, the ability to estimate self-generated distance and duration in individuals with ASD are unclear. We compared the performance of 20 ASD individuals with 20 typical developments (TDs) with respect to two tasks: (1) the drawing of a line of a specified distance (10 or 20 cm) and (2) waiting for a specified time (10 or 20 s). We observed that both the line distances and waiting times were substantially shorter in the ASD group than in the TD group. Furthermore, a trait of "attention to detail," as measured by the Autism-Spectrum Quotient, correlated with some distance and duration productions observed in individuals with ASD. We suggest that attentional functions are related to the contraction of distance and duration in ASD.

A large optical nonlinearity has been observed for the photo-responsive liquid crystals under the condition that the nematic phase is close to the isotropic condition. The direct observation of the photo-response of a liquid crystal by the time-resolved transient grating phase imaging technique revealed that the optical nonlinearity was caused by the transiently generated phase formed inside the photo-induced isotropic region. A shock-like flow was observed for the formation of the transiently generated phase. Based on the theoretical calculation, we propose that a flow generated at the disordered/ordered interface induced the reorientation of the liquid crystal molecules, thereby generating a larger polarization and ultimately causing the optical nonlinearity.

To develop a risk chart or score that is based on recent data and applicable to the Japanese people, we need a large cohort study representative of the Japanese people without a need for long-term follow-up. The purpose of the present study was to develop a risk scoring system to estimate the 5- and 10-year absolute and cumulative incidence risk of stroke and acute myocardial infarction (AMI), composite outcome of stroke and AMI, and death from all cardiovascular disease (CVD). The cumulative incidence risk ratios were calculated using a multiple Poisson regression model and data from the Japan Arteriosclerosis Longitudinal Study, which included 67,969 men and women aged 40-89 years. An absolute risk scoring system for 5- and 10-year risk was developed. For blood pressure categories, the risk ratios for all outcomes increased from normal blood pressure (systolic blood pressure (SBP) 120-129 mmHg and diastolic blood pressure (DBP) 80-89 mmHg) to grade III hypertension (SBP ≥ 180 and/or DBP ≥ 110) based on the 2014 Guidelines for the Management of Hypertension compared to the reference optimal blood pressure (SBP < 120 and DBP < 80). Grade II (SBP 160-179 and/or DBP 100-109) and III hypertension treated with medication showed a lower risk compared to counterparts without medication. Other risk factors showed reasonable figures. The total of scores for each risk factor indicated the estimated absolute risk for stroke and AMI, the composite outcome of stroke and AMI, and all CVD. This scoring system may contribute to patient education and to the development of strategies for reducing CVD in the population.

We report the photochemical carboxylation of o-phenylenedimamine in the absence of a base and an electron donor under an atmosphere of CO 2 , which afforded 2,3-diaminobenzoic acid (DBA) in 28% synthetic yield and 0.22% quantum yield (Φ(%)). The synthetic yield of DBA in this reaction increased to 58% (Φ(%) = 0.47) in the presence of Fe(II). The photochemical reaction described in this work provides an effective strategy to use light as the driving force for the direct carboxylation of organic molecules by CO 2 .

We previously developed a self-cloning system that introduces cDNA of the uridine monophosphate synthase gene (cUMPS) of Coccomyxa sp. strain Obi as a selectable marker into uracil-auxotrophic mutants (Ura - ) of the same alga. Here, we developed a Cre/loxP-based system for the removal of cUMPS flanked by directly repeated loxP sites from the Coccomyxa genome using the intracellular delivery of purified Cre recombinase to generate an Ura - strain that was used as a host for second-round transformation using cUMPS as the selection marker. Employing this marker-gene-recycling system, Coccomyxa strains devoid of foreign DNA except the 34-bp loxP sequence, which overexpressed an acyl-(acyl-carrier-protein) thioesterase gene, and a type-2 diacylglycerol acyltransferase gene, were constructed by the sequential introduction of two expression cassettes for the respective genes. One of the resulting strains showed 1.4-fold higher lipid productivity than the wild-type strain. This method will be applicable to other eukaryotic microalgae to create marker-free transgenic strains.