bluuebunny/crossref_metadata_2025 huggingface dataset:
Ca2+ homeostasis maintained by TMCO1 underlies corpus callosum development via ERK signaling
Authors: Yang Ke-Yan , Zhao Song , Feng Haiping , Shen Jiaqi , Chen Yuwei , Wang Si-Tong , Wang Si-Jia , Zhang Yu-Xin , Wang Yun , Guo Caixia , Liu Hongmei , Tang Tie-Shan
Published: August 2022

Transmembrane of coiled-coil domains 1 (TMCO1) plays an important role in maintaining homeostasis of calcium (Ca2+) stores in the endoplasmic reticulum (ER). TMCO1-defect syndrome shares multiple features with human cerebro-facio-thoracic (CFT) dysplasia, including abnormal corpus callosum (CC). Here, we report that TMCO1 is required for the normal development of CC through sustaining Ca2+homeostasis.Tmco1−/−mice exhibit severe agenesis of CC with stalled white matter fiber bundles failing to pass across the midline. Mechanistically, the excessive Ca2+signals caused by TMCO1 deficiency result in upregulation of FGFs and over-activation of ERK, leading to an excess of glial cell migration and overpopulated midline glia cells in the indusium griseum which secretes Slit2 to repulse extension of the neural fiber bundles before crossing the midline. Supportingly, using the clinical MEK inhibitors to attenuate the over-activated FGF/ERK signaling can significantly improve the CC formation inTmco1−/−brains. Our findings not only unravel the underlying mechanism of abnormal CC in TMCO1 defect syndrome, but also offer an attractive prevention strategy to relieve the related agenesis of CC in patients.
Up-regulation of SLC27A2 suppresses the proliferation and invasion of renal cancer by down-regulating CDK3-mediated EMT
Authors: Xu Ning , Xiao Wen , Meng Xiangui , Li Weiquan , Wang Xuegang , Zhang Xiaoping , Yang Hongmei
Published: August 2022

Clear cell renal cell carcinoma (ccRCC) is one of the most common malignant tumors of the urinary system. Distant metastasis is the leading cause of poor prognosis in ccRCC. However, ccRCC is found poorly responsitive to radiotherapy and chemotherapy. Effective therapeutic strategies for its metastasis remain scarce. We analyzed clinical samples and public database, for differential expression of SLC27A2 and further explored its relationship with clinical prognosis. Biochemistry and functional experiments were carried out to study the potential mechanisms of SLC27A2, CDK3, and EMT. SLC27A2 was significantly downregulated in clinical specimens and renal cancer cell lines and predicted poor prognosis. We found that specific upregulation of SLC27A2 could significantly inhibited the proliferation, migration, and invasion of renal cancer cell lines. SLC27A2 could also influence the Epithelial-mesenchymal transition (EMT) signaling pathway, linked to the progression and metastasis of renal cancer. Using whole transcriptome sequencing of SLC27A2, CDK3 was identified as a regulatory SLC27A2 target. In terms of mechanism, SLC27A2 may further inhibit the epithelial-to-mesenchymal transition by negatively regulating CDK3. Our work suggests that functional inhibition of SLC27A2-CDK3-EMT axis may be an attractive therapeutic target for metastasis of ccRCC.
A comprehensive thermodynamic model for RNA binding by the Saccharomyces cerevisiae Pumilio protein PUF4
Authors: Sadée Christoph , Hagler Lauren D. , Becker Winston R. , Jarmoskaite Inga , Vaidyanathan Pavanapuresan P. , Denny Sarah K. , Greenleaf William J. , Herschlag Daniel
Published: August 2022

Genomic methods have been valuable for identifying RNA-binding proteins (RBPs) and the genes, pathways, and processes they regulate. Nevertheless, standard motif descriptions cannot be used to predict all RNA targets or test quantitative models for cellular interactions and regulation. We present a complete thermodynamic model for RNA binding to the S. cerevisiae Pumilio protein PUF4 derived from direct binding data for 6180 RNAs measured using the RNA on a massively parallel array (RNA-MaP) platform. The PUF4 model is highly similar to that of the related RBPs, human PUM2 and PUM1, with one marked exception: a single favorable site of base flipping for PUF4, such that PUF4 preferentially binds to a non-contiguous series of residues. These results are foundational for developing and testing cellular models of RNA-RBP interactions and function, for engineering RBPs, for understanding the biophysical nature of RBP binding and the evolutionary landscape of RNAs and RBPs.
Homotypic and heterotypic immune responses to Omicron variant in immunocompromised patients in diverse clinical settings
Authors: Ferreira Victor H. , Solera Javier T. , Hu Queenie , Hall Victoria G. , Arbol Berta G. , Rod Hardy W. , Samson Reuben , Marinelli Tina , Ierullo Matthew , Virk Avneet Kaur , Kurtesi Alexandra , Mavandadnejad Faranak , Majchrzak-Kita Beata , Kulasingam Vathany , Gingras Anne-Claude , Kumar Deepali , Humar Atul
Published: August 2022

Immunocompromised patients are predisposed to severe COVID-19. Here we compare homotypic and heterotypic humoral and cellular immune responses to Omicron BA.1 in organ transplant patients across a diverse clinical spectrum. We perform variant-specific pseudovirus neutralization assays for D614G, and Omicron-BA.1, -BA.2, and Delta variants. We also measure poly-and monofunctional T-cell responses to BA.1 and ancestral SARS-CoV-2 peptide pools. We identify that partially or fully-vaccinated transplant recipients after infection with Omicron BA.1 have the greatest BA.1 neutralizing antibody and BA.1-specific polyfunctional CD4+and CD8+T-cell responses, with potent cross-neutralization against BA.2. In these patients, the magnitude of the BA.1-directed response is comparable to immunocompetent triple-vaccinated controls. A subset of patients with pre-Omicron infection have heterotypic responses to BA.1 and BA.2, whereas uninfected transplant patients with three doses of vaccine demonstrate the weakest comparative responses. These results have implications for risk of infection, re-infection, and disease severity among immune compromised hosts with Omicron infection.
TP53-dependent toxicity of CRISPR/Cas9 cuts is differential across genomic loci and can confound genetic screening
Authors: Álvarez Miguel M. , Biayna Josep , Supek Fran
Published: August 2022

CRISPR/Cas9 gene editing can inactivate genes in a precise manner. This process involves DNA double-strand breaks (DSB), which may incur a loss of cell fitness. We hypothesize that DSB toxicity may be variable depending on the chromatin environment in the targeted locus. Here, by analyzing isogenic cell line pair CRISPR experiments jointly with previous screening data from across ~900 cell lines, we show that TP53-associated break toxicity is higher in genomic regions that harbor active chromatin, such as gene regulatory elements or transcription elongation histone marks. DSB repair pathway choice and DNA sequence context also associate with toxicity. We also show that, due to noise introduced by differential toxicity of sgRNA-targeted sites, the power of genetic screens to detect conditional essentiality is reduced in TP53 wild-type cells. Understanding the determinants of Cas9 cut toxicity will help improve design of CRISPR reagents to avoid incidental selection of TP53-deficient and/or DNA repair deficient cells.
Ligand-specific conformational change drives interdomain allostery in Pin1
Authors: Born Alexandra , Soetbeer Janne , Henen Morkos A. , Breitgoff Frauke , Polyhach Yevhen , Jeschke Gunnar , Vögeli Beat
Published: August 2022

Pin1 is a two-domain cell regulator that isomerizes peptidyl-prolines. The catalytic domain (PPIase) and the other ligand-binding domain (WW) sample extended and compact conformations. Ligand binding changes the equilibrium of the interdomain conformations, but the conformational changes that lead to the altered domain sampling were unknown. Prior evidence has supported an interdomain allosteric mechanism. We recently introduced a magnetic resonance-based protocol that allowed us to determine the coupling of intra- and interdomain structural sampling in apo Pin1. Here, we describe ligand-specific conformational changes that occur upon binding of pCDC25c and FFpSPR. pCDC25c binding doubles the population of the extended states compared to the virtually identical populations of the apo and FFpSPR-bound forms. pCDC25c binding to the WW domain triggers conformational changes to propagate via the interdomain interface to the catalytic site, while FFpSPR binding displaces a helix in the PPIase that leads to repositioning of the PPIase catalytic loop.
Impact of adjuvants on the biophysical and functional characteristics of HIV vaccine-elicited antibodies in humans
Authors: Xu Shiwei , Carpenter Margaret C. , Spreng Rachel L. , Neidich Scott D. , Sarkar Sharanya , Tenney DeAnna , Goodman Derrick , Sawant Sheetal , Jha Shalini , Dunn Brooke , Juliana McElrath M. , Bekker Valerie , Mudrak Sarah V. , Flinko Robin , Lewis George K. , Ferrari Guido , Tomaras Georgia D. , Shen Xiaoying , Ackerman Margaret E.
Published: August 2022

Adjuvants can alter the magnitude, characteristics, and persistence of the humoral response to protein vaccination. HIV vaccination might benefit from tailored adjuvant choice as raising a durable and protective response to vaccination has been exceptionally challenging. Analysis of trials of partially effective HIV vaccines have identified features of the immune response that correlate with decreased risk, including high titers of V1V2-binding IgG and IgG3 responses with low titers of V1V2-binding IgA responses and enhanced Fc effector functions, notably antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). However, there has been limited opportunity to compare the effect of different adjuvants on these activities in humans. Here, samples from the AVEG015 study, a phase 1 trial in which participants (n = 112) were immunized with gp120SF-2and one of six different adjuvants or combinations thereof were assessed for antibody titer, biophysical features, and diverse effector functions. Three adjuvants, MF59 + MTP-PE, SAF/2, and SAF/2 + MDP, increased the peak magnitude and durability of antigen-specific IgG3, IgA, FcγR-binding responses and ADCP activity, as compared to alum. While multiple adjuvants increased the titer of IgG, IgG3, and IgA responses, none consistently altered the balance of IgG to IgA or IgG3 to IgA. Linear regression analysis identified biophysical features including gp120-specific IgG and FcγR-binding responses that could predict functional activity, and network analysis identified coordinated aspects of the humoral response. These analyses reveal the ability of adjuvants to drive the character and function of the humoral response despite limitations of small sample size and immune variability in this human clinical trial.
Single mutation makes Escherichia coli an insect mutualist
Authors: Koga Ryuichi , Moriyama Minoru , Onodera-Tanifuji Naoko , Ishii Yoshiko , Takai Hiroki , Mizutani Masaki , Oguchi Kohei , Okura Reiko , Suzuki Shingo , Gotoh Yasuhiro , Hayashi Tetsuya , Seki Masahide , Suzuki Yutaka , Nishide Yudai , Hosokawa Takahiro , Wakamoto Yuichi , Furusawa Chikara , Fukatsu Takema
Published: August 2022

Microorganisms often live in symbiosis with their hosts, and some are considered mutualists, where all species involved benefit from the interaction. How free-living microorganisms have evolved to become mutualists is unclear. Here we report an experimental system in which non-symbiotic Escherichia coli evolves into an insect mutualist. The stinkbug Plautia stali is typically associated with its essential gut symbiont, Pantoea sp., which colonizes a specialized symbiotic organ. When sterilized newborn nymphs were infected with E. coli rather than Pantoea sp., only a few insects survived, in which E. coli exhibited specific localization to the symbiotic organ and vertical transmission to the offspring. Through transgenerational maintenance with P. stali, several hypermutating E. coli lines independently evolved to support the host’s high adult emergence and improved body colour; these were called ‘mutualistic’ E. coli. These mutants exhibited slower bacterial growth, smaller size, loss of flagellar motility and lack of an extracellular matrix. Transcriptomic and genomic analyses of ‘mutualistic’ E. coli lines revealed independent mutations that disrupted the carbon catabolite repression global transcriptional regulator system. Each mutation reproduced the mutualistic phenotypes when introduced into wild-type E. coli, confirming that single carbon catabolite repression mutations can make E. coli an insect mutualist. These findings provide an experimental system for future work on host–microbe symbioses and may explain why microbial mutualisms are omnipresent in nature.
Near-real-time MODIS-derived vegetation index data products and online services for CONUS based on NASA LANCE
Authors: Zhang Chen , Yang Zhengwei , Di Liping , Yu Eugene G. , Zhang Bei , Han Weiguo , Lin Li , Guo Liying
Published: August 2022

This paper describes a set of Near-Real-Time (NRT) Vegetation Index (VI) data products for the Conterminous United States (CONUS) based on Moderate Resolution Imaging Spectroradiometer (MODIS) data from Land, Atmosphere Near-real-time Capability for EOS (LANCE), an openly accessible NASA NRT Earth observation data repository. The data set offers a variety of commonly used VIs, including Normalized Difference Vegetation Index (NDVI), Vegetation Condition Index (VCI), Mean-referenced Vegetation Condition Index (MVCI), Ratio to Median Vegetation Condition Index (RMVCI), and Ratio to previous-year Vegetation Condition Index (RVCI). LANCE enables the NRT monitoring of U.S. cropland vegetation conditions within 24 hours of observation. With more than 20 years of observations, this continuous data set enables geospatial time series analysis and change detection in many research fields such as agricultural monitoring, natural resource conservation, environmental modeling, and Earth system science. The complete set of VI data products described in the paper is openly distributed via Web Map Service (WMS) and Web Coverage Service (WCS) as well as the VegScape web application (https://nassgeodata.gmu.edu/VegScape/).
Childhood individual and family modifiable risk factors for criminal conviction: a 7-year cohort study from Brazil
Authors: Ziebold Carolina , Evans-Lacko Sara , Andrade Mário César Rezende , Hoffmann Maurício Scopel , Fonseca Lais , Barbosa Matheus Ghossain , Pan Pedro Mario , Miguel Euripedes , Bressan Rodrigo Affonseca , Rohde Luis Augusto , Salum Giovanni Abrahão , de Jesus Mari Jair , Gadelha Ary
Published: August 2022

Crime is a major public problem in low- and middle-income countries (LMICs) and its preventive measures could have great social impact. The extent to which multiple modifiable risk factors among children and families influence juvenile criminal conviction in an LMIC remains unexplored; however, it is necessary to identify prevention targets. This study examined the association between 22 modifiable individual and family exposures assessed in childhood (5–14 years, n = 2511) and criminal conviction at a 7-year follow-up (13–21 years, n = 1905, 76% retention rate) in a cohort of young people in Brazil. Population attributable risk fraction (PARF) was computed for significant risk factors. Criminal convictions were reported for 81 (4.3%) youths. Although most children living in poverty did not present criminal conviction (89%), poverty at baseline was the only modifiable risk factor significantly associated with crime (OR 4.14, 99.8% CI 1.38–12.46) with a PARF of 22.5% (95% CI 5.9–36.1%). It suggests that preventing children’s exposure to poverty would reduce nearly a quarter of subsequent criminal convictions. These findings highlight the importance of poverty in criminal conviction, as it includes several deprivations and suggest that poverty eradication interventions during childhood may be crucial for reducing crime among Brazilian youth.
Consistent trait-temperature interactions drive butterfly phenology in both incidental and survey data
Authors: Larsen Elise A. , Belitz Michael W. , Guralnick Robert P. , Ries Leslie
Published: August 2022

Data availability limits phenological research at broad temporal and spatial extents. Butterflies are among the few taxa with broad-scale occurrence data, from both incidental reports and formal surveys. Incidental reports have biases that are challenging to address, but structured surveys are often limited seasonally and may not span full flight phenologies. Thus, how these data source compare in phenological analyses is unclear. We modeled butterfly phenology in relation to traits and climate using parallel analyses of incidental and survey data, to explore their shared utility and potential for analytical integration. One workflow aggregated “Pollard” surveys, where sites are visited multiple times per year; the other aggregated incidental data from online portals: iNaturalist and eButterfly. For 40 species, we estimated early (10%) and mid (50%) flight period metrics, and compared the spatiotemporal patterns and drivers of phenology across species and between datasets. For both datasets, inter-annual variability was best explained by temperature, and seasonal emergence was earlier for resident species overwintering at more advanced stages. Other traits related to habitat, feeding, dispersal, and voltinism had mixed or no impacts. Our results suggest that data integration can improve phenological research, and leveraging traits may predict phenology in poorly studied species.
Distributed encoding of curvilinear self-motion across spiral optic flow patterns
Authors: Layton Oliver W. , Fajen Brett R.
Published: August 2022

Self-motion along linear paths without eye movements creates optic flow that radiates from the direction of travel (heading). Optic flow-sensitive neurons in primate brain area MSTd have been linked to linear heading perception, but the neural basis of more general curvilinear self-motion perception is unknown. The optic flow in this case is more complex and depends on the gaze direction and curvature of the path. We investigated the extent to which signals decoded from a neural model of MSTd predict the observer’s curvilinear self-motion. Specifically, we considered the contributions of MSTd-like units that were tuned to radial, spiral, and concentric optic flow patterns in “spiral space”. Self-motion estimates decoded from units tuned to the full set of spiral space patterns were substantially more accurate and precise than those decoded from units tuned to radial expansion. Decoding only from units tuned to spiral subtypes closely approximated the performance of the full model. Only the full decoding model could account for human judgments when path curvature and gaze covaried in self-motion stimuli. The most predictive units exhibited bias in center-of-motion tuning toward the periphery, consistent with neurophysiology and prior modeling. Together, findings support a distributed encoding of curvilinear self-motion across spiral space.
EKF-SIRD model algorithm for predicting the coronavirus (COVID-19) spreading dynamics
Authors: Sebbagh Abdennour , Kechida Sihem
Published: August 2022

In this paper, we study the Covid 19 disease profile in the Algerian territory since February 25, 2020 to February 13, 2021. The idea is to develop a decision support system allowing public health decision and policy-makers to have future statistics (the daily prediction of parameters) of the pandemic; and also encourage citizens for conducting health protocols. Many studies applied traditional epidemic models or machine learning models to forecast the evolution of coronavirus epidemic, but the use of such models alone to make the prediction will be less precise. For this purpose, we assume that the spread of the coronavirus is a moving target described by an epidemic model. On the basis of a SIRD model (Susceptible-Infection-Recovery- Death), we applied the EKF algorithm to predict daily all parameters. These predicted parameters will be much beneficial to hospital managers for updating the available means of hospitalization (beds, oxygen concentrator, etc.) in order to reduce the mortality rate and the infected. Simulations carried out reveal that the EKF seems to be more efficient according to the obtained results.
Effects of landscape structure on restoration success in tropical premontane forest
Authors: San-José Miriam , Werden Leland K. , Joyce Francis H. , Reid J. Leighton , Holl Karen D. , Zahawi Rakan A.
Published: August 2022

Reversing large-scale habitat degradation and deforestation goes beyond what can be achieved by site-level ecological restoration and a landscape ecology perspective is fundamental. Here we assess the relative importance of tree cover and its configuration on forest-dependent birds and late-successional tree seedlings in restoration sites in southern Costa Rica. The abundance and species richness of birds increased in landscapes with more corridors, higher tree cover, and lower levels of fragmentation, highlighting the importance of riparian corridors for connectivity, and continuous tree cover as suitable habitat. Landscape variables affected abundance and species richness of seedlings similarly, but effects were weaker, possibly because seedlings face establishment limitation in addition to dispersal limitation. Moreover, the scale of landscape effects on seedlings was small, likely because proximal individual trees can significantly influence recruitment in restoration plots. Results underscore the importance of incorporating landscape-level metrics to restoration projects, as knowing the extent, and how the landscape may affect restoration outcomes can help to infer what kind of species will arrive to restoration plots.
A new marsh beetle from mid-Cretaceous amber of northern Myanmar (Coleoptera: Scirtidae)
Authors: Li Yan-Da , Ruta Rafał , Tihelka Erik , Liu Zhen-Hua , Huang Di-Ying , Cai Chen-Yang
Published: August 2022

As one of the earliest-diverging lineage of the megadiverse beetle suborder Polyphaga, marsh beetles (Scirtidae) are crucial for reconstructing the ancestor of all polyphagan beetles and the ecomorphological underpinnings of their remarkable evolutionary success. The phylogeny of marsh beetles has nonetheless remained challenging to infer, not least because of their fragmentary Mesozoic fossil record. Here we describe a new scirtid beetle genus and species,Varcalium lawrenceigen. et sp. nov., preserving internal tissue, from Albian–Cenomanian Kachin amber (ca99 Ma), representing the second member of this family known from the deposit. Based on a formal morphological phylogenetic analysis,Varcaliumis recovered within the crown-group of Scirtinae, forming a clade with other genera that possess subocular carinae. The finding suggests that the crown-group of Scirtinae has already diversified by the mid-Cretaceous.
Including state-of-the-art physical understanding of thermal vacancies in Calphad models
Authors: Obaied A. , Roslyakova I. , To Baben M.
Published: August 2022

A physically sound thermochemical model accounting for explicit thermal vacancies in elements and alloys is presented. The model transfers the latest theoretical understanding of vacancy formation into the Calphad formalism where it can extend currently available thermodynamic databases to cover vacancy concentrations without a complete re-assessment. The parametrization of the model is based on ab initio-calculated enthalpy of vacancy formation and two model parameters describing the excess heat capacity of vacancy formation. Excellent agreement is obtained with temperature-dependent vacancy concentrations and elemental heat capacities while reasonable extrapolation of phase stability to high temperatures is ensured. Extrapolation to multicomponent systems is reasonable and the long-standing Neumann–Kopp related problem in the Calphad community is solved since multicomponent solid solutions will no longer show fingerprints of elemental heat capacity peaks at their melting points. FCC-Ag, FCC-Al and FCC-Cu, FCC-Zn, FCC-Ni, BCC-Ti, and BCC-W are used as a demonstration, along with the Cu–Zn binary system.
Improving plane wave ultrasound imaging through real-time beamformation across multiple arrays
Authors: Foiret Josquin , Cai Xiran , Bendjador Hanna , Park Eun-Yeong , Kamaya Aya , Ferrara Katherine W.
Published: August 2022

Ultrasound imaging is a widely used diagnostic tool but has limitations in the imaging of deep lesions or obese patients where the large depth to aperture size ratio (f-number) reduces image quality. Reducing the f-number can improve image quality, and in this work, we combined three commercial arrays to create a large imaging aperture of 100 mm and 384 elements. To maintain the frame rate given the large number of elements, plane wave imaging was implemented with all three arrays transmitting a coherent wavefront. On wire targets at a depth of 100 mm, the lateral resolution is significantly improved; the lateral resolution was 1.27 mm with one array (1/3 of the aperture) and 0.37 mm with the full aperture. After creating virtual receiving elements to fill the inter-array gaps, an autoregressive filter reduced the grating lobes originating from the inter-array gaps by − 5.2 dB. On a calibrated commercial phantom, the extended field-of-view and improved spatial resolution were verified. The large aperture facilitates aberration correction using a singular value decomposition-based beamformer. Finally, after approval of the Stanford Institutional Review Board, the three-array configuration was applied in imaging the liver of a volunteer, validating the potential for enhanced resolution.
Fully integrated topological electronics
Authors: Liu Yuqi , Cao Weidong , Chen Weijian , Wang Hua , Yang Lan , Zhang Xuan
Published: August 2022

Topological insulators (TIs) have attracted significant attention in photonics and acoustics due to their unique physical properties and promising applications. Electronics has recently emerged as an exciting arena to study various topological phenomena because of its advantages in building complex topological structures. Here, we explore TIs on an integrated circuit (IC) platform with a standard complementary metal-oxide-semiconductor technology. Based on the Su–Schrieffer–Heeger model, we design a fully integrated topological circuit chain using multiple capacitively-coupled inductor–capacitor resonators. We perform comprehensive post-layout simulations on its physical layout to observe and evaluate the salient topological features. Our results demonstrate the existence of the topological edge state and the remarkable robustness of the edge state against various defects. Our work shows the feasibility and promise of studying TIs with IC technology, paving the way for future explorations of large-scale topological electronics on the scalable IC platform.
A computational modelling study of excitation of neuronal cells with triboelectric nanogenerators
Authors: Nazari-Vanani Razieh , Mohammadpour Raheleh , Asadian Elham , Rafii-Tabar Hashem , Sasanpour Pezhman
Published: August 2022

Neurological disorders and nerve injuries, such as spinal cord injury, stroke, and multiple sclerosis can result in the loss of muscle function. Electrical stimulation of the neuronal cells is the currently available clinical treatment in this regard. As an effective energy harvester, the triboelectric nanogenerators (TENG) can be used for self-powered neural/muscle stimulations because the output of the TENG provides stimulation pulses for nerves. In the present study, using a computational modelling approach, the effect of surface micropatterns on the electric field distribution, induced voltage and capacitance of the TENG structures have been investigated. By incorporating the effect of the TENG inside the mathematical model of neuron’s electrical behavior (cable equation with Hodgkin-Huxley model), its impact on the electrical behavior of the neurons has been studied. The results show that the TENG operates differently with various surface modifications. The performance of the TENG in excitation of neurons depends on the contact and release speed of its electrodes accordingly.
Gastruloids as in vitro models of embryonic blood development with spatial and temporal resolution
Authors: Rossi Giuliana , Giger Sonja , Hübscher Tania , Lutolf Matthias P.
Published: August 2022

Gastruloids are three-dimensional embryonic organoids that reproduce key features of early mammalian development in vitro with unique scalability, accessibility, and spatiotemporal similarity to real embryos. Recently, we adapted the gastruloid culture conditions to promote cardiovascular development. In this work, we extended these conditions to capture features of embryonic blood development through a combination of immunophenotyping, detailed transcriptomics analysis, and identification of blood stem/progenitor cell potency. We uncovered the emergence of blood progenitor and erythroid-like cell populations in late gastruloids and showed the multipotent clonogenic capacity of these cells, both in vitro and after transplantation into irradiated mice. We also identified the spatial localization near a vessel-like plexus in the anterior portion of gastruloids with similarities to the emergence of blood stem cells in the mouse embryo. These results highlight the potential and applicability of gastruloids to the in vitro study of complex processes in embryonic blood development with spatiotemporal fidelity.
Role of Sr doping and external strain on relieving bottleneck of oxygen diffusion in La2−xSrxCuO4−δ
Authors: Park Sohee , Kwon Young-Kyun , Yoon Mina , Park Changwon
Published: August 2022

In many complex oxides, the oxygen vacancy formation is a promising route to modify the material properties such as a superconductivity and an oxygen diffusivity. Cation substitutions and external strain have been utilized to control the concentration and diffusion of oxygen vacancies, but the mechanisms behind the controls are not fully understood. Using first-principles calculations, we find how Sr doping and external strain greatly enhances the diffusivity of oxygen vacancies in La2−xSrxCuO4−δ (LSCO) in the atomic level. In hole-doped case (2x > δ), the formation energy of an apical vacancy in the LaO layer is larger than its equatorial counterpart by 0.2 eV that the bottleneck of diffusion process is for oxygen vacancies to escape equatorial sites. Such an energy difference can be reduced and even reversed by either small strain (< 1.5%) or short-range attraction between Sr and oxygen vacancy, and in turn, the oxygen diffusivity is greatly enhanced. For fully compensated hole case (2x ≦ δ), the formation energy of an apical vacancy becomes too high that most oxygen vacancies cannot move but would be trapped at equatorial sites. From our electronic structure analysis, we found that the contrasting change in the formation energy by Sr doping and external strain is originated from the different localization natures of electron carrier from both types of oxygen vacancies.
A validation of the two-high threshold eyewitness identification model by reanalyzing published data
Authors: Menne Nicola Marie , Winter Kristina , Bell Raoul , Buchner Axel
Published: August 2022

The two-high threshold (2-HT) eyewitness identification model serves as a new measurement tool to measure the latent cognitive processes underlying eyewitness identification performance. By simultaneously taking into account correct culprit identifications, false innocent-suspect identifications, false filler identifications in culprit-present and culprit-absent lineups as well as correct and false lineup rejections, the model capitalizes on the full range of data categories that are observed when measuring eyewitness identification performance. Thereby, the model is able to shed light on detection-based and non-detection-based processes underlying eyewitness identification performance. Specifically, the model incorporates parameters for the detection of culprit presence and absence, biased selection of the suspect and guessing-based selection among the lineup members. Here, we provide evidence of the validity of each of the four model parameters by applying the model to eight published data sets. The data sets come from studies with experimental manipulations that target one of the underlying processes specified by the model. Manipulations of encoding difficulty, lineup fairness and pre-lineup instructions were sensitively reflected in the parameters reflecting culprit-presence detection, biased selection and guessing-based selection, respectively. Manipulations designed to facilitate the rejection of culprit-absent lineups affected the parameter for culprit-absence detection. The reanalyses of published results thus suggest that the parameters sensitively reflect the manipulations of the processes they were designed to measure, providing support of the validity of the 2-HT eyewitness identification model.
Relationships between genome-wide R-loop distribution and classes of recurrent DNA breaks in neural stem/progenitor cells
Authors: Thongthip Supawat , Carlson Annika , Crossley Magdalena P. , Schwer Bjoern
Published: August 2022

Recent studies revealed classes of recurrent DNA double-strand breaks (DSBs) in neural stem/progenitor cells, including transcription-associated, promoter-proximal breaks and recurrent DSB clusters in late-replicating, long neural genes that may give rise to somatic brain mosaicism. The mechanistic factors promoting these different classes of DSBs in neural stem/progenitor cells are not understood. Here, we elucidated the genome-wide landscape of RNA:DNA hybrid structures called “R-loops” in primary neural stem/progenitor cells undergoing aphidicolin-induced, mild replication stress to assess the potential contribution of R-loops to the different, recurrent classes of DNA break “hotspots”. We find that R-loops in neural stem/progenitor cells undergoing mild replication stress are present primarily in early-replicating, transcribed regions and in genes with promoter GC skew that are associated with cell lineage-specific processes. Surprisingly, most long, neural genes that form recurrent DSB clusters do not show R-loop formation under conditions of mild replication stress. Our findings are consistent with a role of R-loop-associated processes in promoter-proximal DNA break formation in highly transcribed, early replicating regions but suggest that R-loops do not drive replication stress-induced, recurrent DSB cluster formation in most long, neural genes.
The trend in adoption of hearing aids following changes in provision policy in South Korea
Authors: Byun Hayoung , Kim Eun Mi , Kim Inah , Lee Seung Hwan , Chung Jae Ho
Published: August 2022

The Korean government started to cover part of the price of hearing aids ($200) for individuals with hearing disabilities in 1997, and the reimbursement for a hearing aid increased in 2005 ($300) and again in 2015 ($1000). The aim of this study was to evaluate the annual trend of newly-registered individuals with hearing disability according to the changes of the hearing aid provision scheme. Subjects with newly-registered hearing disabilities were assessed using Korean National Health Insurance Service (KNHIS) data from January 1, 2004, to December 31, 2018. A total of 271,742 individuals were newly registered during the index period. Records of hearing aid prescriptions and hearing aid subsidies were used to assess the adoption of hearing aids. This study also assessed the intervals between registration of hearing disability and the adoption of hearing aids, as well as the number of hearing aid subsidies provided. From 2004 to 2009 there was a slight increase in the number of individuals newly registered with hearing disabilities, and from 2011 to 2015, the number showed a tendency to decrease. Then, from 2015, the number of individuals with hearing disabilities increased abruptly, and the proportion of subjects receiving hearing aid subsidies also increased. Between 2004 and 2018, the time interval from hearing disability registration to hearing aid adoption showed a decreasing trend. We conclude that the annual number of individuals with newly-registered hearing disabilities is affected by the level of the hearing aid subsidy, and there is much unregistered or unaddressed hearing loss prior to the introduction of realistic hearing aid provision.
Tunable Brownian magneto heat pump
Authors: Abdoli Iman , Wittmann René , Brader Joseph Michael , Sommer Jens-Uwe , Löwen Hartmut , Sharma Abhinav
Published: August 2022

We propose a mesoscopic Brownian magneto heat pump made of a single charged Brownian particle that is steered by an external magnetic field. The particle is subjected to two thermal noises from two different heat sources. When confined, the particle performs gyrating motion around a potential energy minimum. We show that such a magneto-gyrator can be operated as both a heat engine and a refrigerator. The maximum power delivered by the engine and the performance of the refrigerator, namely the rate of heat transferred per unit external work, can be tuned and optimised by the applied magnetic field. Further tunability of the key properties of the engine, such as the direction of gyration and the torque exerted by the engine on the confining potential, is obtained by varying the strength and direction of the applied magnetic field. In principle, our predictions can be tested by experiments with colloidal particles and complex plasmas.
Development of mixed starter culture for the fermentation of Ethiopian honey wine, Tej
Authors: Fentie Eskindir Getachew , Jeong Minsoo , Emire Shimelis Admassu , Demsash Hundessa Dessalegn , Kim Min-Chul , Lim Kyeongmo , Shin Jae-Ho
Published: August 2022

Ethiopian honey wine is one of the country's most popular spontaneously fermented traditional alcoholic beverages. However, the final product of this natural fermentation system is frequently of poor and inconsistent quality. Furthermore, it makes the process difficult to predict, control, and correct. Thus, the main aim of this study was to develop a direct fermentation system for Ethiopian honey wine, Tej. After isolating fermentative microbial strains from Tej samples, they were subjected to intensive screening to fit to its purpose. Later, phenotypic and genotypic characterization, and inoculation of isolates to honey-must were performed sequentially. Finally, microbial interaction and physicochemical analysis, including volatile compounds profiling, were done for the inoculated samples. The identified isolates were strains of Saccharomycetaceae and Lactobacillaceae families. These strains showed a good ability to tolerate osmotic stress and a lower pH environment. Tej sample produced by mixed culture inoculation of Saccharomyces and Lactobacillus species showed similar physicochemical, volatile compounds, and sensory attributes values with that of the control sample. Thus, a mixture of Saccharomyces and Lactobacillus strains could be used as a starter culture to produce Ethiopian honey, Tej, without scarifying of its major quality attributes.
Comparative study of different liquid diets for dairy calves and the impact on performance and the bacterial community during diarrhea
Authors: Coelho Marina Gavanski , Virgínio Júnior Gercino Ferreira , Tomaluski Cristiane Regina , de Toledo Ariany Faria , Reis Maria Eduarda , Dondé Sophia Cattleya , Mendes Lucas William , Coutinho Luiz Lehmann , Bittar Carla Maris Machado
Published: August 2022

The liquid diet composition can affect dairy calves' performance and diarrhea incidence. The effect of three liquid diets on performance, incidence of diarrhea, and microbial community during diarrhea occurrence in dairy calves were evaluated. At birth, 35 dairy calves (20 male and 15 female) were randomly assigned to one of three treatments—refrigerated whole milk (WM), acidified whole milk (AWM), and milk replacer (MR). Intake, fecal score, and rectal temperature were evaluated daily, and performance and blood parameters were evaluated weekly during the preweaning period. Fecal samples from diarrheic calves were collected, and one initial and one final sample for each episode were selected. The bacterial community was assessed by sequencing the V3-V4 region of the 16S rRNA gene on the Illumina MiSeq platform and analyzed using the DADA2 pipeline. Calves fed WM had higher body weight at weaning, average daily gain, body measurements, and concentration of blood metabolites. The AWM-fed calves had a lower rectal temperature and fever days. Moreover, the MR-fed calves had lower beta-hydroxybutyrate concentration and a higher incidence of diarrhea. The fecal bacterial community of diarrheic calves showed dissimilarity among the AWM and the other treatments. At the compositional level, we observed a higher abundance ofFusobacteriumandRuminococcusgenera (AWM),Prevotella(WM), andLactobacillus(MR). In the AWM and MR diarrheic calves' feces, we also observed some beneficial bacterial genera. The performance and incidence of diarrhea of dairy calves were influenced by the liquid diet consumed and the bacterial composition of diarrhea.
Randomly fluctuating neural connections may implement a consolidation mechanism that explains classic memory laws
Authors: Murre Jaap M. J.
Published: August 2022

How can we reconcile the massive fluctuations in neural connections with a stable long-term memory? Two-photon microscopy studies have revealed that large portions of neural connections (spines, synapses) are unexpectedly active, changing unpredictably over time. This appears to invalidate the main assumption underlying the majority of memory models in cognitive neuroscience, which rely on stable connections that retain information over time. Here, we show that such random fluctuations may in fact implement a type of memory consolidation mechanism with a stable very long-term memory that offers novel explanations for several classic memory ‘laws’, namely Jost’s Law (1897: superiority of spaced learning) and Ribot’s Law (1881: loss of recent memories in retrograde amnesia), for which a common neural basis has been postulated but not established, as well as other general ‘laws’ of learning and forgetting. We show how these phenomena emerge naturally from massively fluctuating neural connections.
A comparative study on selectivity and sensitivity of new chromium and copper electrodes
Authors: Bakhshi Sarabi Elnaz , Hajiaghababaei Leila , Allahgholi Ghasri Mohammad Reza , Mottaghinejad Seyed Enayatollah , Parsa Ali
Published: August 2022

4-Methylcoumarin-7-yloxy-N-phenyl acetamide and 4-methylcoumarin-7-yloxy-N-4-nitrophenyl acetamide were synthesized and used as new ionophores in the carbon paste matrix to produce two novel potentiometric modified electrodes. The selectivity of the electrode changed from copper (II) to chromium (III) with the addition of a nitro group to the phenyl ring of the ionophore. The ionophores’ tendency to ions was confirmed by UV–visible spectrophotometry. Both electrodes were modified by multi-walled carbon nanotubes (MWCNTs) as an excellent modifier of carbon paste electrode (CPE). The best sensor response in the case of copper (II) selective CPE was obtained by 5% ionophore, 65% graphite powder, 5% MWCNT, and 25% paraffin oil. In addition, in the case of chromium (III) selective CPE, these conditions are 20% ionophore, 50% graphite powder, 5% MWCNT, and 25% paraffin oil. The copper (II) selective CPE showed a Nernstian slope of 32.15 mV/decade within the concentration range of 1.0 × 10–10–1.0 × 10–1 mol L−1, while chromium (III) selective CPE showed a Nernstian slope of 19.28 mV/decade over the concentration range of 1.0 × 10–10–7.0 × 10–3 mol L−1. The electrodes have short response time of less than 5 s and were used successfully to determine copper (II) in wastewater and to speciation of chromium (III) and chromium (VI).
Cathodoluminescence imaging of cellular structures labeled with luminescent iridium or rhenium complexes at cryogenic temperatures
Authors: Vancová Marie , Skoupý Radim , Ďurinová Eva , Bílý Tomáš , Nebesářová Jana , Krzyžánek Vladislav , Kolouch Aleš , Horodyský Petr
Published: August 2022

We report for the first time the use of two live-cell imaging agents from the group of luminescent transition metal complexes (IRAZOLVE-MITO and REZOLVE-ER) as cathodoluminescent probes. This first experimental demonstration shows the application of both probes for the identification of cellular structures at the nanoscale and near the native state directly in the cryo-scanning electron microscope. This approach can potentially be applied to correlative and multimodal approaches and used to target specific regions within vitrified samples at low electron beam energies.
Nuclear β-catenin translocation plays a key role in osteoblast differentiation of giant cell tumor of bone
Authors: Kimura Atsushi , Toda Yu , Matsumoto Yoshihiro , Yamamoto Hidetaka , Yahiro Kenichiro , Shimada Eijiro , Kanahori Masaya , Oyama Ryunosuke , Fukushima Suguru , Nakagawa Makoto , Setsu Nokitaka , Endo Makoto , Fujiwara Toshifumi , Matsunobu Tomoya , Oda Yoshinao , Nakashima Yasuharu
Published: August 2022

Denosumab is a game-changing drug for giant cell tumor of bone (GCTB); however, its clinical biomarker regarding tumor ossification of GCTB has not been elucidated. In this study, we investigated the relationship between Wnt/β-catenin signaling and the ossification of GCTB and evaluated whether endogenous nuclear β-catenin expression predicted denosumab-induced bone formation in GCTB. Genuine patient-derived primary GCTB tumor stromal cells exhibited osteoblastic characteristics. Identified osteoblastic markers and nuclear β-catenin translocation were significantly upregulated via differentiation induction and were inhibited by treating with Wnt signaling inhibitor, GGTI-286, or selective Rac1-LEF inhibitor, NSC23766. Furthermore, we reviewed the endogenous ossification and nuclear β-catenin translocation of 86 GCTB clinical samples and elucidated that intra-tumoral ossification was significantly associated with the nuclear translocation. Three-dimensional quantitative analyses (n = 13) of tumoral CT images have revealed that the nuclear β-catenin translocation of naïve GCTB samples was significantly involved with the denosumab-induced tumor ossification. Our findings suggest a close relationship between the nuclear β-catenin translocation and the osteoblastic differentiation of GCTB. Investigations of the nuclear β-catenin in naïve GCTB samples may provide a promising biomarker for predicting the ossification of GCTB following denosumab treatment.
Risk factors of dermatophytosis among Korean adults
Authors: Son Joon Ho , Doh Jee Yun , Han Kyungdo , Kim Yeong Ho , Han Ju Hee , Bang Chul Hwan , Park Young Min , Lee Ji Hyun
Published: August 2022

Dermatophytosis includes all fungal infections caused by dermatophytes in humans. Some risk factors for the development of subtypes of dermatophytosis have been studied; however, large-scale epidemiologic studies on risk factors for total dermatophytosis are scarce. We investigated the risk factors of dermatophytosis using a nationwide study. Total 4,532,655 subjects with dermatophytosis aged between 20 and 40 years were examined using data from the Korean National Health Insurance Service from 2009 to 2018. Women showed a lower risk of development of dermatophytosis compared to men [hazard ratio (HR) 0.848; 95% confidence interval (CI) 0.843–0.853]. Subjects with elevated waist circumference (HR 1.057; 95% CI 1.048–1.065), heavy drinking (HR 1.053; 95% CI 1044–1.061), engaging in mild-to-heavy exercise (HR 1.071; 95% CI 1.064–1.077) had a higher risk of dermatophytosis. In addition, subjects with body mass index (BMI) of more than 30 kg/m2 exhibited a higher risk of dermatophytosis (HR 1.36; 95% CI 1.342–1.378) compared to those with BMIs in the range of 18.5–23 kg/m2. In this study, the risk of developing dermatophytosis significantly increased in individuals with elevated waist circumference or high BMI. Lifestyle modifications, including weight management, are suggested to be important in preventing dermatophytosis.