bluuebunny/crossref_metadata_2025 huggingface dataset:
Detection and Localization of Eu on Biosilica by Analytical Scanning Electron Microscopy
Authors: Hieckmann Ellen , Kammerlander Kaitlin K K , Köhler Lydia , Neumann Laura , Saager Stefan , Albanis Nico , Hutsch Thomas , Seifert Frank , Brunner Eike
Published: September 2021

Algae like diatoms are widely studied as a means to remediate anthropogenically contaminated sites. In the present study, CL (cathodoluminescence) and EDX (energy-dispersive X-ray) spectroscopy in an SEM (scanning electron microscope) were optimized for the detection of Eu(III) sorbed on diatom biosilica. The required stability of biosilica under a focused electron beam was extensively investigated. Using experimentally determined data of thermal properties, the temperature increase within biosilica exposed to an electron beam was simulated by finite element calculations based on results from Monte Carlo simulations of electron scattering. Complementary thermogravimetric studies substantiated a chemical stability of biosilica in a wide temperature range, confirming its suitability for long-lasting SEM investigations. In subsequent EDX measurements, characteristic Eu lines were detected. Eu was found to preferentially accumulate and aggregate on silica fragments. CL spectra were obtained for the Eu(III) reference material, EuCl3. For Eu-loaded biosilica, even parts without detectable Eu signal in the EDX spectra show significant Eu(III) signals in the CL spectra. This highlights the sensitivity of CL in studying f-element sorption. CL data showed that Eu(III) was distributed on the entire surface. In conclusion, this work demonstrates the merit of CL and EDX methods for sorption studies on biogenic materials.
The Rule of Climate Policy: How Do Chinese Judges Contribute to Climate Governance without Climate Law?
Authors: Zhu Mingzhe
Published: September 2021

China's climate governance is distinguished by the contrast between an abundance of policies on climate change and the lack of legally binding laws. This article argues that Chinese courts bridge this difference, which fosters a ‘rule of climate policy’ rather than a strict rule of law. The effective authority of Chinese climate policy is made possible in practice both by provisions of the Chinese Constitution and the prevailing use of legal reasoning. China's constitutional design of ‘ecological civilization’ delegates the duty and the power of managing climate change issues to the executive branch of its government. Most Chinese documents on climate governance have no binding legal force, which means, according to positive law, that they cannot serve as legal grounds for judicial decisions. Chinese judges, in deciding climate-related disputes, must combine legal provisions and non-binding materials to achieve regulatory goals. They use non-legal materials to support statutory or contractual interpretations and determine the existence or limits of rights, which alters the meaning and scope of existing legal terms and principles. This rule of climate policy is possible in the courtroom because judges justify public policy considerations with arguments of principle that are substantiated in various non-binding climate plans.
Impact of Langmuir Turbulence, Wave Breaking, and Stokes Drift on Upper Ocean Dynamics Under Hurricane Conditions
Authors: Hughes Colin J. , Liu Guoqiang , Perrie William , Sheng Jinyu
Published: September 2021

Ocean surface gravity waves can modulate the upper ocean circulation and vertical mixing through air‐sea interactions, wave breaking, Coriolis‐Stokes forcing, Langmuir turbulence and the grid resolved vortex force. However, the roles of these wave induced processes remain uncertain under hurricane conditions. This study examines the impact of these surface wave associated dynamics on the turbulent kinetic energy (TKE), thermal structure and currents in the upper ocean under idealized hurricane forcing using a coupled wave‐circulation model. Eight experiments were conducted with hurricanes moving at three translational speeds. The simulations include two fully coupled experiments and five additional coupled experiments in which wave effects are selectively disabled. All coupled experiments are compared with a baseline circulation simulation. Consistent with previous studies, our results indicate that Langmuir turbulence has the biggest impact on upper ocean currents, temperature and TKE during hurricanes. However, all considered wave effects contribute to vertical mixing and the two‐way fully coupled experiment differs the most from the baseline experiment. The combined wave effects reduce the surface currents by over 0.8 m/s in the front two quadrants of the slow hurricane and enhance the cold wake and near‐surface cooling by as much as 0.6°C, predominantly to the right of the storm track. The wave contributions to the cooling are inversely related to the hurricane translational speed, although their contributions to currents and TKE are correlated with hurricane translational speed. SST differences can alter the latent heat flux driving hurricanes, suggesting that wave dynamics should be included in hurricane forecast models.
Functional independence in the Finnish spinal cord injury population
Authors: Majamäki Kirsi , Tallqvist Susanna , Vainionpää Aki , Koskinen Eerika , Kauppila Anna-Maija , Bergman Paula , Anttila Heidi , Hämäläinen Harri , Täckman Anni , Kallinen Mauri , Arokoski Jari , Hiekkala Sinikka
Published: September 2021

Study design

A cross-sectional survey of the Finnish population with spinal cord injury (FinSCI database).

Objectives

To describe the functional independence of the population with spinal cord injury (SCI) in Finland and to identify how generic and lesion characteristics affect their functional independence.

Setting

The participants were recruited from the registers of three SCI outpatient clinics responsible for lifelong follow-up and care for people with SCI in Finland.

Methods

The data were retrieved from FinSCI (n = 1772). The response rate was 50% (n = 884). The Spinal Cord Independence Measure-Self Report (SCIM-SR) was used. The data were analyzed with univariate testing, factor analyses, and multiple linear regression models.

Results

The median (percentiles 25; 75) SCIM-SR total score was 76.0 (58.8; 89.0), and the score was 18.0 (13.0; 20:0) for the self-care sub-scale, 33.0 (25.0; 39.0) for the respiration and sphincter management sub-scale and 29.0 (16.0; 36.8) for the mobility sub-scale. The higher the neurological level in groups AIS A, B, and C, the lower the functional ability. Group AIS D at any injury level had the highest level of functional ability. Age and the number of years since injury negatively influenced the SCIM-SR scores for every sub-scale.

Conclusion

Based on the International Spinal Cord Injury Core Data Set, the severity of SCI can differentiate persons with SCI according to their functional ability. The results suggest that SCI affects individuals’ health more than ageing alone does, thereby reducing the functional ability and independence of persons with SCI over time.
Cortical structure and the risk for Alzheimer’s disease: a bidirectional Mendelian randomization study
Authors: Wu Bang-Sheng , Zhang Ya-Ru , Li Hong-Qi , Kuo Kevin , Chen Shi-Dong , Dong Qiang , Liu Yong , Yu Jin-Tai
Published: September 2021

Progressive loss of neurons in a specific brain area is one of the manifestations of Alzheimer’s disease (AD). Much effort has been devoted to investigating brain atrophy and AD. However, the causal relationship between cortical structure and AD is not clear. We conducted a bidirectional two-sample Mendelian randomization analysis to investigate the causal relationship between cortical structure (surface area and thickness of the whole cortex and 34 cortical regions) and AD risk. Genetic variants used as instruments came from a large genome-wide association meta-analysis of cortical structure (33,992 participants of European ancestry) and AD (AD and AD-by-proxy, 71,880 cases, 383,378 controls). We found suggestive associations of the decreased surface area of the temporal pole (OR (95% CI): 0.95 (0.9, 0.997), p = 0.04), and decreased thickness of cuneus (OR (95% CI): 0.93 (0.89, 0.98), p = 0.006) with higher AD risk. We also found a suggestive association of vulnerability to AD with the decreased surface area of precentral (β (SE): –43.4 (21.3), p = 0.042) and isthmus cingulate (β (SE): –18.5 (7.3), p = 0.011). However, none of the Bonferroni-corrected p values of the causal relationship between cortical structure and AD met the threshold. We show suggestive evidence of an association of the atrophy of the temporal pole and cuneus with higher AD risk. In the other direction, there was a suggestive causal relationship between vulnerability to AD and the decreased surface area of the precentral and isthmus cingulate. Our findings shed light on the associations of cortical structure with the occurrence of AD.
The LOVD3 platform: efficient genome-wide sharing of genetic variants
Authors: Fokkema Ivo F.A.C. , Kroon Mark , López Hernández Julia A. , Asscheman Daan , Lugtenburg Ivar , Hoogenboom Jerry , den Dunnen Johan T.
Published: September 2021

Gene variant databases are the backbone of DNA-based diagnostics. These databases, also called Locus-Specific DataBases (LSDBs), store information on variants in the human genome and the observed phenotypic consequences. The largest collection of public databases uses the free, open-source LOVD software platform. To cope with the current demand for online databases, we have entirely redesigned the LOVD software. LOVD3 is genome-centered and can be used to store summary variant data, as well as full case-level data with information on individuals, phenotypes, screenings, and variants. While built on a standard core, the software is highly flexible and allows personalization to cope with the largely different demands of gene/disease database curators. LOVD3 follows current standards and includes tools to check variant descriptions, generate HTML files of reference sequences, predict the consequences of exon deletions/duplications on the reading frame, and link to genomic views in the different genomes browsers. It includes APIs to collect and submit data. The software is used by about 100 databases, of which 56 public LOVD instances are registered on our website and together contain 1,000,000,000 variant observations in 1,500,000 individuals. 42 LOVD instances share data with the federated LOVD data network containing 3,000,000 unique variants in 23,000 genes. This network can be queried directly, quickly identifying LOVD instances containing relevant information on a searched variant.
Fatal attraction of Caenorhabditis elegans to predatory fungi through 6-methyl-salicylic acid
Authors: Yu Xi , Hu Xiaodi , Pop Maria , Wernet Nicole , Kirschhöfer Frank , Brenner-Weiß Gerald , Keller Julia , Bunzel Mirko , Fischer Reinhard
Published: September 2021

Salicylic acid is a phenolic phytohormone which controls plant growth and development. A methyl ester (MSA) derivative thereof is volatile and involved in plant-insect or plant-plant communication. Here we show that the nematode-trapping fungus Duddingtonia flagrans uses a methyl-salicylic acid isomer, 6-MSA as morphogen for spatiotemporal control of trap formation and as chemoattractant to lure Caenorhabditis elegans into fungal colonies. 6-MSA is the product of a polyketide synthase and an intermediate in the biosynthesis of arthrosporols. The polyketide synthase (ArtA), produces 6-MSA in hyphal tips, and is uncoupled from other enzymes required for the conversion of 6-MSA to arthrosporols, which are produced in older hyphae. 6-MSA and arthrosporols both block trap formation. The presence of nematodes inhibits 6-MSA and arthrosporol biosyntheses and thereby enables trap formation. 6-MSA and arthrosporols are thus morphogens with some functions similar to quorum-sensing molecules. We show that 6-MSA is important in interkingdom communication between fungi and nematodes.
Achieving ultrahigh instantaneous power density of 10 MW/m2 by leveraging the opposite-charge-enhanced transistor-like triboelectric nanogenerator (OCT-TENG)
Authors: Wu Hao , Wang Steven , Wang Zuankai , Zi Yunlong
Published: September 2021

Converting various types of ambient mechanical energy into electricity, triboelectric nanogenerator (TENG) has attracted worldwide attention. Despite its ability to reach high open-circuit voltage up to thousands of volts, the power output of TENG is usually meager due to the high output impedance and low charge transfer. Here, leveraging the opposite-charge-enhancement effect and the transistor-like device design, we circumvent these limitations and develop a TENG that is capable of delivering instantaneous power density over 10 MW/m2 at a low frequency of ~ 1 Hz, far beyond that of the previous reports. With such high-power output, 180 W commercial lamps can be lighted by a TENG device. A vehicle bulb containing LEDs rated 30 W is also wirelessly powered and able to illuminate objects further than 0.9 meters away. Our results not only set a record of the high-power output of TENG but also pave the avenues for using TENG to power the broad practical electrical appliances.
The slow self-arresting nature of low-frequency earthquakes
Authors: Wei Xueting , Xu Jiankuan , Liu Yuxiang , Chen Xiaofei
Published: September 2021

Low-frequency earthquakes are a series of recurring small earthquakes that are thought to compose tectonic tremors. Compared with regular earthquakes of the same magnitude, low-frequency earthquakes have longer source durations and smaller stress drops and slip rates. The mechanism that drives their unusual type of stress accumulation and release processes is unknown. Here, we use phase diagrams of rupture dynamics to explore the connection between low-frequency earthquakes and regular earthquakes. By comparing the source parameters of low-frequency earthquakes from 2001 to 2016 in Parkfield, on the San Andreas Fault, with those from numerical simulations, we conclude that low-frequency earthquakes are earthquakes that self-arrest within the rupture patch without any introduced interference. We also explain the scaling property of low-frequency earthquakes. Our findings suggest a framework for fault deformation in which nucleation asperities can release stress through slow self-arrest processes.
Murine femur micro-computed tomography and biomechanical datasets for an ovariectomy-induced osteoporosis model
Authors: Stephens Maialen , López-Linares Karen , Aldazabal Javier , Macias Iratxe , Ortuzar Naiara , Bengoetxea Harkaitz , Bulnes Susana , Alcorta-Sevillano Natividad , Infante Arantza , Lafuente Jose Vicente , Rodríguez Clara I.
Published: September 2021

The development of new effective and safer therapies for osteoporosis, in addition to improved diagnostic and prevention strategies, represents a serious need in the scientific community. Micro-CT image-based analyses in association with biomechanical testing have become pivotal tools in identifying osteoporosis in animal models by assessment of bone microarchitecture and resistance, as well as bone strength. Here, we describe a dataset of micro-CT scans and reconstructions of 15 whole femurs and biomechanical tests on contralateral femurs from C57BL/6JOlaHsd ovariectomized (OVX), resembling human post-menopausal osteoporosis, and sham operated (sham) female mice. Data provided for each mouse include: the acquisition images (.tiff), the reconstructed images (.bmp) and an.xls file containing the maximum attenuations for each reconstructed image. Biomechanical data include an.xls file with the recorded load-displacement, a movie with the filmed test and an.xls file collecting all biomechanical results.
Directional wave buoy data measured near Campbell Island, New Zealand
Authors: McComb Peter , Garrett Sally , Durrant Tom , Perez Jorge
Published: September 2021

The New Zealand Defence Force (NZDF) has established a permanent wave observation station near Campbell Island, south of New Zealand (52 45.71 S, 169 02.54E). The site was chosen for logistical convenience and its unique location adjacent to the highly energetic Southern Ocean; allowing instrumentation typically deployed on the continental shelf to be used in this rarely observed southern environment. From February 2017, a Triaxys Directional Wave Buoy was moored in 147 m depth, some 17 km to the south of the island, with satellite telemetry of the 2D wave spectra at 3-hourly intervals. To date there have been three deployments on locations, yielding some 784 days of data. Validation of the measured significant wave height against co-located satellite altimeter observations suggests that the predominant wave directions are not attenuated by the island. The data provide a valuable record of the detailed wave spectral characteristics from one of the least-sampled parts of the Global Ocean.
The multilevel organismal diversity approach deciphers difficult to distinguish nudibranch species complex
Authors: Korshunova Tatiana A. , Driessen Floor M. F. , Picton Bernard E. , Martynov Alexander V.
Published: September 2021

Species identification is a key procedure for broad-scoped ecological, phylogeographic and evolutionary studies. However, to perform a taxonomic study in the molecular era is a complicated task that has many pitfalls. In the present study we use particular examples of common but difficult to distinguish European species within the genus of Polycera (Nudibranchia, Mollusca) to discuss the general issues of the “cryptic species” problem that has broad biological and interdisciplinary importance and can significantly impede ecological, evolutionary, and other biodiversity-related research. The largest dataset of molecular and morphological information for European nudibranchs ever applied encompasses a wide geographical area and shapes a robust framework in this study. Four species are recognized in the species complex, including a new one. It is shown that a lack of appropriate taxonomic analysis led recently to considerable errors in species identity assessment of this complex. Chromatic polymorphism for each species is mapped in a periodic-like framework and combined with statistical analysis of the diagnostic features that considerably facilitates identification of particular species in the complex for biologists and practitioners. The present study evidently shows that “cryptic” and “non-cryptic” components are present within the same species. Therefore, this species complex is well suited for the exploring and testing of general biological problems. One of the main conclusions of this study is that division of biological diversity into “cryptic” and “non-cryptic” components is counterproductive. We propose that the central biological phenomenon of a species can instead be universally designated as multilevel organismal diversity thereby provide a practical set of methods for its investigation.
X-linked immunodeficient (XID) mice exhibit high susceptibility to Cryptococcus gattii infection
Authors: Diniz-Lima Israel , da Rosa Pablo Rodrigo , da Silva-Junior Elias Barbosa , Guimarães-de-Oliveira Joyce Cristina , de Freitas Elisangela Oliveira , de Oliveira Nascimento Danielle , Morrot Alexandre , Nimrichter Leonardo , Previato Jose Osvaldo , Mendonça-Previato Lucia , Freire-de-Lima Leonardo , Decote-Ricardo Debora , Freire-de-Lima Celio Geraldo
Published: September 2021

Cryptococcosis is an opportunistic disease caused by the fungus Cryptococcus neoformans and Cryptococcus gattii. It starts as a pulmonary infection that can spread to other organs, such as the brain, leading to the most serious occurrence of the disease, meningoencephalitis. The humoral response has already been described in limiting the progression of cryptococcosis where the B-1 cell seems to be responsible for producing natural IgM antibodies, crucial for combating fungal infections. The role of the B-1 cell in C. neoformans infection has been initially described, however the role of the humoral response of B-1 cells has not yet been evaluated during C. gattii infections. In the present study we tried to unravel this issue using XID mice, a murine model deficient in the Btk protein which compromises the development of B-1 lymphocytes. We use the XID mice compared to BALB/c mice that are sufficient for the B-1 population during C. gattii infection. Our model of chronic lung infection revealed that XID mice, unlike the sufficient group of B-1, had early mortality with significant weight loss, in addition to reduced levels of IgM and IgG specific to GXM isolated from the capsule of C. neoformans. In addition to this, we observed an increased fungal load in the blood and in the brain. We described an increase in the capsular size of C. gattii and the predominant presence of cytokines with a Th2 profile was also observed in these animals. Thus, the present study strongly points to a higher susceptibility of the XID mouse to C. gattii, which suggests that the presence of B-1 cells and anti-GXM antibodies is fundamental during the control of infection by C. gattii.
Jianpi Qushi Heluo Formula alleviates renal damages in Passive Hemann nephritis in rats by upregulating Parkin-mediated mitochondrial autophagy
Authors: Wang Xin-hui , Lang Rui , Zeng Qin , Liang Ying , Chen Nan , Ma Zhi-zhong , Yu Ren-huan
Published: September 2021

Jianpi Qushi Heluo Formula (JQHF) is an empirical traditional Chinese medicine prescription for treating Membranous Nephropathy (MN) clinically in China. The therapeutic effect of JQHF has been reported in our previous studies. However, the exact mechanism is still unknown. In this study, by establishing an experimental rat model of MN induced by Sheep anti-rat Fx1A serum, we evaluated the effects of JQHF and Tetrandrine (TET), and Benazepril was used as a positive control. As an autophagy agonist, TET is one of the most active components in JQHF. After 4 weeks, significant kidney damage was observed in the rats in the Model group; comparatively, JQHF markedly decreased 24 h urinary protein, Total Cholesterol (TC), and increased serum total Albumin (ALB). Histology showed that JQHF caused significant improvements in glomerular hyperplasia, renal tubular damage, IgG immune complex deposition, and the ultrastructure of mitochondria in MN rats. Flow cytometry analysis showed that treatment with JQHF reduced the level of reactive oxygen species and apoptosis rate, and upregulated mitochondrial membrane potential. Western blot analysis demonstrated that JQHF could protect against mitochondrial dysfunction and apoptosis by upregulating the expression of PINK1, Mitochondrial Parkin, and LC3-II/I, downregulating the expression of Cytoplasmic Parkin, P62, Cytochrome c, and Caspase-3 in the kidneys of MN rats. From images of co-immunofluorescence, it is observed significantly increase in the co-localization of PINK1 and Parkin, as well as LC3 and mitochondria. Similarly, TET treatment significantly upregulated the mitochondrial autophagy and reduced apoptosis in rats after 4 weeks compared with the model group. Comparatively, the ability of JQHF to alleviate renal damage was significantly higher than those of Benazepril and TET. It was demonstrated that JQHF could delay pathology damage to the kidney and hold back from the progression of MN by inhibiting apoptosis and upregulating the mitochondrial autophagy by PINK1/Parkin pathways.
Terahertz time-domain ellipsometry with high precision for the evaluation of GaN crystals with carrier densities up to 1020 cm−3
Authors: Agulto Verdad C. , Iwamoto Toshiyuki , Kitahara Hideaki , Toya Kazuhiro , Mag-usara Valynn Katrine , Imanishi Masayuki , Mori Yusuke , Yoshimura Masashi , Nakajima Makoto
Published: September 2021

Gallium nitride (GaN) is one of the most technologically important semiconductors and a fundamental component in many optoelectronic and power devices. Low-resistivity GaN wafers are in demand and actively being developed to improve the performance of vertical GaN power devices necessary for high-voltage and high-frequency applications. For the development of GaN devices, nondestructive characterization of electrical properties particularly for carrier densities in the order of 1019 cm−3 or higher is highly favorable. In this study, we investigated GaN single crystals with different carrier densities of up to 1020 cm−3 using THz time-domain ellipsometry in reflection configuration. The p- and s-polarized THz waves reflected off the GaN samples are measured and then corrected based on the analysis of multiple waveforms measured with a rotating analyzer. We show that performing such analysis leads to a ten times higher precision than by merely measuring the polarization components. As a result, the carrier density and mobility parameters can be unambiguously determined even at high conductivities.
Role of myeloid cell leptin signaling in the regulation of glucose metabolism
Authors: Pereira Sandra , Cline Daemon L. , Chan Melissa , Chai Kalin , Yoon Ji Soo , O’Dwyer Shannon M. , Ellis Cara E. , Glavas Maria M. , Webber Travis D. , Baker Robert K. , Erener Suheda , Covey Scott D. , Kieffer Timothy J.
Published: September 2021

Although innate immunity is linked to metabolic health, the effect of leptin signaling in cells from the innate immune system on glucose homeostasis has not been thoroughly investigated. We generated two mouse models using Cre-lox methodology to determine the effect of myeloid cell-specific leptin receptor (Lepr) reconstitution and Lepr knockdown on in vivo glucose metabolism. Male mice with myeloid cell-specific Lepr reconstitution (Lyz2Cre+LeprloxTB/loxTB) had better glycemic control as they aged compared to male mice with whole-body transcriptional blockade of Lepr (Lyz2Cre−LeprloxTB/loxTB). In contrast, Lyz2Cre+LeprloxTB/loxTB females only had a trend for diminished hyperglycemia after a prolonged fast. During glucose tolerance tests, Lyz2Cre+LeprloxTB/loxTB males had a mildly improved plasma glucose profile compared to Cre− controls while Lyz2Cre+LeprloxTB/loxTB females had a similar glucose excursion to their Cre− controls. Myeloid cell-specific Lepr knockdown (Lyz2Cre+Leprflox/flox) did not significantly alter body weight, blood glucose, insulin sensitivity, or glucose tolerance in males or females. Expression of the cytokine interleukin 10 (anti-inflammatory) tended to be higher in adipose tissue of male Lyz2Cre+LeprloxTB/loxTB mice (p = 0.0774) while interleukin 6 (pro-inflammatory) was lower in male Lyz2Cre+Leprflox/flox mice (p < 0.05) vs. their respective controls. In conclusion, reconstitution of Lepr in cells of myeloid lineage has beneficial effects on glucose metabolism in male mice.
Multi-omics analysis to decipher the molecular link between chronic exposure to pollution and human skin dysfunction
Authors: Misra Namita , Clavaud Cécile , Guinot Florent , Bourokba Nasrine , Nouveau Stephanie , Mezzache Sakina , Palazzi Paul , Appenzeller Brice M. R. , Tenenhaus Arthur , Leung Marcus H. Y. , Lee Patrick K. H. , Bastien Philippe , Aguilar Luc , Cavusoglu Nükhet
Published: September 2021

Environmental pollution is composed of several factors, namely particulate matter (PM2.5, PM10), ozone and Ultra Violet (UV) rays among others and first and the most exposed tissue to these substances is the skin epidermis. It has been established that several skin disorders such as eczema, acne, lentigines and wrinkles are aggravated by exposure to atmospheric pollution. While pollutants can interact with skin surface, contamination of deep skin by ultrafine particles or Polycyclic aromatic hydrocarbons (PAH) might be explained by their presence in blood and hair cortex. Molecular mechanisms leading to skin dysfunction due to pollution exposure have been poorly explored in humans. In addition to various host skin components, cutaneous microbiome is another target of these environment aggressors and can actively contribute to visible clinical manifestation such as wrinkles and aging. The present study aimed to investigate the association between pollution exposure, skin microbiota, metabolites and skin clinical signs in women from two cities with different pollution levels. Untargeted metabolomics and targeted proteins were analyzed from D-Squame samples from healthy women (n = 67 per city), aged 25–45 years and living for at least 15 years in the Chinese cities of Baoding (used as a model of polluted area) and Dalian (control area with lower level of pollution). Additional samples by swabs were collected from the cheeks from the same population and microbiome was analysed using bacterial 16S rRNA as well as fungal ITS1 amplicon sequencing and metagenomics analysis. The level of exposure to pollution was assessed individually by the analysis of polycyclic aromatic hydrocarbons (PAH) and their metabolites in hair samples collected from each participant. All the participants of the study were assessed for the skin clinical parameters (acne, wrinkles, pigmented spots etc.). Women from the two cities (polluted and less polluted) showed distinct metabolic profiles and alterations in skin microbiome. Profiling data from 350 identified metabolites, 143 microbes and 39 PAH served to characterize biochemical events that correlate with pollution exposure. Finally, using multiblock data analysis methods, we obtained a potential molecular map consisting of multi-omics signatures that correlated with the presence of skin pigmentation dysfunction in individuals living in a polluted environment. Overall, these signatures point towards macromolecular alterations by pollution that could manifest as clinical sign of early skin pigmentation and/or other imperfections.
A MATLAB-based program for three-dimensional quantitative analysis of micronuclei reveals that neuroinflammation induces micronuclei formation in the brain
Authors: Yano Sarasa , Akiyama Kaito , Tsuchiya Rio , Kubotani Hikari , Chiba Tomoki , Nagata Takeshi , Tsuruta Fuminori
Published: September 2021

The micronucleus is known to be a biomarker for genomic instability, which is a hallmark of tumors and aging. Normally, micronuclei are produced by segregation errors and mechanical stresses arising from dividing or migrating cells, leading to activation of the innate immune response pathway. Although micronuclei often emerge in damaged tissues, the quantitative procedure for analyzing micronuclei accurately has been problematic. Here, we introduce a novel MATLAB-based program for quantifying micronuclei (CAMDi: calculating automatic micronuclei distinction) in vitro and in vivo. CAMDi is adaptable to various experimental imaging techniques and is useful for obtaining reproducible data. CAMDi enables us to measure the accurate size of micronuclei from the three-dimensional images. Using CAMDi, we revealed a novel link between the emergence of micronuclei and neuroinflammation. We found that inflammatory stimulation does not increase the number of micronuclei in primary neurons. On the other hand, the administration of lipopolysaccharide into mice slightly increases micronuclei formation in neurons of the hippocampus region. These findings demonstrate that neuronal micronuclei formations are induced by an inflammatory response in a non-cell-autonomous manner. We provide a novel tool, CAMDi, to quantify micronuclei and demonstrate that neuronal micronuclei are produced not only by the cell-autonomous process but also by the intercellular communication associated with neuroinflammation in vivo.
Spontaneous emergence of leadership patterns drives synchronization in complex human networks
Authors: Calabrese Carmela , Lombardi Maria , Bollt Erik , De Lellis Pietro , Bardy Benoît G. , di Bernardo Mario
Published: September 2021

Synchronization of human networks is fundamental in many aspects of human endeavour. Recently, much research effort has been spent on analyzing how motor coordination emerges in human groups (from rocking chairs to violin players) and how it is affected by coupling structure and strength. Here we uncover the spontaneous emergence of leadership (based on physical signaling during group interaction) as a crucial factor steering the occurrence of synchronization in complex human networks where individuals perform a joint motor task. In two experiments engaging participants in an arm movement synchronization task, in the physical world as well as in the digital world, we found that specific patterns of leadership emerged and increased synchronization performance. Precisely, three patterns were found, involving a subtle interaction between phase of the motion and amount of influence. Such patterns were independent of the presence or absence of physical interaction, and persisted across manipulated spatial configurations. Our results shed light on the mechanisms that drive coordination and leadership in human groups, and are consequential for the design of interactions with artificial agents, avatars or robots, where social roles can be determinant for a successful interaction.
A gain series method for accurate EMCCD calibration
Authors: Ryan Duncan P. , Dunlap Megan K. , Gelfand Martin P. , Werner James H. , Van Orden Alan K. , Goodwin Peter M.
Published: September 2021

Calibration of the gain and digital conversion factor of an EMCCD is necessary for accurate photon counting. We present a new method to quickly calibrate multiple gain settings of an EMCCD camera. Acquiring gain-series calibration data and analyzing the resulting images with the EMCCD noise model more accurately estimates the gain response of the camera. Furthermore, we develop a method to compare the results from different calibration approaches. Gain-series calibration outperforms all other methods in this self-consistency test.
Empagliflozin maintains capillarization and improves cardiac function in a murine model of left ventricular pressure overload
Authors: Nakao Masaaki , Shimizu Ippei , Katsuumi Goro , Yoshida Yohko , Suda Masayoshi , Hayashi Yuka , Ikegami Ryutaro , Hsiao Yung Ting , Okuda Shujiro , Soga Tomoyoshi , Minamino Tohru
Published: September 2021

Patients with type 2 diabetes treated with Sodium glucose transporter 2 (SGLT2) inhibitors show reduced mortality and hospitalization for heart failure (HF). SGLT2 inhibitors are considered to activate multiple cardioprotective pathways; however, underlying mechanisms are not fully described. This study aimed to elucidate the underlying mechanisms of the beneficial effects of SGLT2 inhibitors on the failing heart. We generated a left ventricular (LV) pressure overload model in C57BL/6NCrSlc mice by transverse aortic constriction (TAC) and examined the effects of empagliflozin (EMPA) in this model. We conducted metabolome and transcriptome analyses and histological and physiological examinations. EMPA administration ameliorated pressure overload-induced systolic dysfunction. Metabolomic studies showed that EMPA increased citrulline levels in cardiac tissue and reduced levels of arginine, indicating enhanced metabolism from arginine to citrulline and nitric oxide (NO). Transcriptome suggested possible involvement of the insulin/AKT pathway that could activate NO production through phosphorylation of endothelial NO synthase (eNOS). Histological examination of the mice showed capillary rarefaction and endothelial apoptosis after TAC, both of which were significantly improved by EMPA treatment. This improvement was associated with enhanced expression phospho-eNOS and NO production in cardiac endothelial cells. NOS inhibition attenuated these cardioprotective effects of EMPA. The in vitro studies showed that catecholamine-induced endothelial apoptosis was inhibited by NO, arginine, or AKT activator. EMPA activates the AKT/eNOS/NO pathway, which helps to suppress endothelial apoptosis, maintain capillarization and improve systolic dysfunction during LV pressure overload.
Glycyrrhizin ameliorating sterile inflammation induced by low-dose radiation exposure
Authors: Kim Hyung Cheol , Oh Hyewon , You Je Sung , Chung Yong Eun
Published: September 2021

Glycyrrhizin (GL) is a direct inhibitor of HMGB1 which acts as an alarmin when excreted into the extracellular space. High-dose radiation in radiotherapy induces collateral damage to the normal tissue, which can be mitigated by GL inhibiting HMGB1. The purpose of this study was to assess changes in HMGB1 and pro-inflammatory cytokines and to evaluate the protective effect of GL after low-dose radiation exposure. BALB/c mice were irradiated with 0.1 Gy (n = 10) and 1 Gy (n = 10) with GL being administered to half of the mice (n = 5, respectively) before irradiation. Blood and spleen samples were harvested and assessed for oxidative stress, HMGB1, pro-inflammatory cytokines, and cell viability. HMGB1 and pro-inflammatory cytokines increased and cell viability decreased after irradiation in a dose-dependent manner. Oxidative stress also increased after irradiation, but did not differ between 0.1 Gy and 1 Gy. With the pretreatment of GL, oxidative stress, HMGB1, and all of the pro-inflammatory cytokines decreased while cell viability was preserved. Our findings indicate that even low-dose radiation can induce sterile inflammation by increasing serum HMGB1 and pro-inflammatory cytokines and that GL can ameliorate the sterile inflammatory process by inhibiting HMGB1 to preserve cell viability.
Asialoglycoprotein receptor targeted optical and magnetic resonance imaging and therapy of liver fibrosis using pullulan stabilized multi-functional iron oxide nanoprobe
Authors: Saraswathy Ariya , Nazeer Shaiju S. , Nimi Nirmala , Santhakumar Hema , Suma Parvathy Radhakrishnapillai , Jibin Kunnumpurathu , Victor Marina , Fernandez Francis Boniface , Arumugam Sabareeswaran , Shenoy Sachin J. , Varma P. R. Harikrishna , Jayasree Ramapurath S.
Published: September 2021

Early diagnosis and therapy of liver fibrosis is of utmost importance, especially considering the increased incidence of alcoholic and non-alcoholic liver syndromes. In this work, a systematic study is reported to develop a dual function and biocompatible nanoprobe for liver specific diagnostic and therapeutic applications. A polysaccharide polymer, pullulan stabilized iron oxide nanoparticle (P-SPIONs) enabled high liver specificity via asialogycoprotein receptor mediation. Longitudinal and transverse magnetic relaxation rates of 2.15 and 146.91 mM−1 s−1 respectively and a size of 12 nm, confirmed the T2 weighted magnetic resonance imaging (MRI) efficacy of P-SPIONs. A current of 400A on 5 mg/ml of P-SPIONs raised the temperature above 50 °C, to facilitate effective hyperthermia. Finally, a NIR dye conjugation facilitated targeted dual imaging in liver fibrosis models, in vivo, with favourable histopathological results and recommends its use in early stage diagnosis using MRI and optical imaging, and subsequent therapy using hyperthermia.
Method of estimating the effective zone induced by rapid impact compaction
Authors: Cheng Shih-Hao , Chen Shi-Shuenn , Ge Louis
Published: September 2021

This paper proposes a method for estimating the effective zone, including effective depth and effective range of compaction degree, from rapid impact compaction (RIC) on sand layer whose fines content is less than 10%. The proposed method utilizes a string of microelectromechanical system accelerometers to monitor the acceleration at various depths and propagation distances during compaction. To interpret and extract useful information from monitored data, peak-over-threshold (POT) processing and normal distribution function were used to analyze the recorded acceleration. The mean and standard deviation of the threshold peak acceleration were used to evaluate the effective depth and the effective range of compaction degree during RIC compaction. Moreover, spatial contours were used to determine the correlation of the threshold peak acceleration against depth and propagation distance from the RIC impact point. These contours help indicating the distribution of the effect zone after compaction. Lastly, a proposed method is suggested for frequent use in trial tests to quickly determine RIC’s required depth and impact spacing.
Clinicopathological characteristics and prognosis of hepatitis B associated membranous nephropathy and idiopathic membranous nephropathy complicated with hepatitis B virus infection
Authors: Wang Ruiqiang , Wu Yunqi , Zheng Bowen , Zhang Xiaofeng , An Dongyue , Guo Ningning , Wang Jin , Guo Yuanyuan , Tang Lin
Published: September 2021

The main objective of this study is to analyze the clinical and pathological features and prognosis of patients with Hepatitis B associated membranous nephropathy (HBV-MN) and idiopathic membranous nephropathy (IMN) complicated with hepatitis B virus (HBV) infection. This study will provide more basis for diagnosis and prognosis evaluation. A total of 50 patients with HBV-MN were included in this study. 56 IMN patients complicated with HBV infection diagnosed during the same period formed the control group. Parameters including blood routine, urine routine and plasma levels of albumin (ALB), serum creatinine (SCR), blood urea nitrogen (BUN), urea acid (UA), total cholesterol (T-CHO), triglycerides (TG), complement C3 and C4, glutamic pyruvic transaminase (ALT), glutamic pyruvic transaminase (AST), 24-h urinary protein quantification (24 h-TP), renal phospholipase A2 receptor (PLA2R) and HBV related markers during the hospitalization and outpatient follow-up study period were collected for all the patients. The proportion of male patients was high in both groups. The average age of the HBV-MN group was 37.2 ± 14.187 years old, it was younger compared with the IMN group (P = 0.003). Nephrotic syndrome was the major clinical manifestation among patients. There was no significant difference between the two groups in the levels of anemia, microscopic hematuria, renal dysfunction, liver dysfunction, liver cirrhosis. The level of serum C3 and C4 in the HBV-MN group was lower compared with the IMN group (P = 0.002, P = 0.014). In the HBV-MN group, serum HBV markers were negative in 6 (12%) patients, 4 patients (8%) were positive for PLA2R in serum, and 5 patients (10%) were positive for PLA2R in renal tissue. Stronger IgG1 and C1q and weaker IgG4 staining were found in HBV-MN group renal tissues (P = 0.003, P = 0.025, and P = 0.001, respectively). There were no statistical differences compared with serum and renal PLA2R between HBV-MN and IMN groups (P = 0.098, P = 0.109). During the 1-year follow-up, there was no significant difference in complete remission rate between the two groups (P = 0.7739). Renal biopsy is crucial to diagnose HBV-MN. IgG subtypes in the HBV-MN group were mainly IgG1 deposition, while those in IMN complicated with HBV infection group were mainly IgG4 deposition. When HBV-associated antigen and PLA2R are present in renal tissue, lower level of serum C3 and C4, high intensity of renal C1q and IgG1 is more supportive of HBV-MN. The positive of PLA2R in serum and renal tissue in differentiating HBV from IMN complicated with HBV infection remains to be discussed.
Measurement of respiratory rate using wearable devices and applications to COVID-19 detection
Authors: Natarajan Aravind , Su Hao-Wei , Heneghan Conor , Blunt Leanna , O’Connor Corey , Niehaus Logan
Published: September 2021

We show that heart rate enabled wearable devices can be used to measure respiratory rate. Respiration modulates the heart rate creating excess power in the heart rate variability at a frequency equal to the respiratory rate, a phenomenon known as respiratory sinus arrhythmia. We isolate this component from the power spectral density of the heart beat interval time series, and show that the respiratory rate thus estimated is in good agreement with a validation dataset acquired from sleep studies (root mean squared error = 0.648 min−1, mean absolute error = 0.46 min−1, mean absolute percentage error = 3%). We use this respiratory rate algorithm to illuminate two potential applications (a) understanding the distribution of nocturnal respiratory rate as a function of age and sex, and (b) examining changes in longitudinal nocturnal respiratory rate due to a respiratory infection such as COVID-19. 90% of respiratory rate values for healthy adults fall within the range 11.8−19.2 min−1 with a mean value of 15.4 min−1. Respiratory rate is shown to increase with nocturnal heart rate. It also varies with BMI, reaching a minimum at 25 kg/m2, and increasing for lower and higher BMI. The respiratory rate decreases slightly with age and is higher in females compared to males for age <50 years, with no difference between females and males thereafter. The 90% range for the coefficient of variation in a 14 day period for females (males) varies from 2.3–9.2% (2.3−9.5%) for ages 20−24 yr, to 2.5−16.8% (2.7−21.7%) for ages 65−69 yr. We show that respiratory rate is often elevated in subjects diagnosed with COVID-19. In a 7 day window from D−1 to D+5 (where D0 is the date when symptoms first present, for symptomatic individuals, and the test date for asymptomatic cases), we find that 36.4% (23.7%) of symptomatic (asymptomatic) individuals had at least one measurement of respiratory rate 3 min−1 higher than the regular rate.
Non-invasive diagnosis of deep vein thrombosis from ultrasound imaging with machine learning
Authors: Kainz Bernhard , Heinrich Mattias P. , Makropoulos Antonios , Oppenheimer Jonas , Mandegaran Ramin , Sankar Shrinivasan , Deane Christopher , Mischkewitz Sven , Al-Noor Fouad , Rawdin Andrew C. , Ruttloff Andreas , Stevenson Matthew D. , Klein-Weigel Peter , Curry Nicola
Published: September 2021

Deep vein thrombosis (DVT) is a blood clot most commonly found in the leg, which can lead to fatal pulmonary embolism (PE). Compression ultrasound of the legs is the diagnostic gold standard, leading to a definitive diagnosis. However, many patients with possible symptoms are not found to have a DVT, resulting in long referral waiting times for patients and a large clinical burden for specialists. Thus, diagnosis at the point of care by non-specialists is desired. We collect images in a pre-clinical study and investigate a deep learning approach for the automatic interpretation of compression ultrasound images. Our method provides guidance for free-hand ultrasound and aids non-specialists in detecting DVT. We train a deep learning algorithm on ultrasound videos from 255 volunteers and evaluate on a sample size of 53 prospectively enrolled patients from an NHS DVT diagnostic clinic and 30 prospectively enrolled patients from a German DVT clinic. Algorithmic DVT diagnosis performance results in a sensitivity within a 95% CI range of (0.82, 0.94), specificity of (0.70, 0.82), a positive predictive value of (0.65, 0.89), and a negative predictive value of (0.99, 1.00) when compared to the clinical gold standard. To assess the potential benefits of this technology in healthcare we evaluate the entire clinical DVT decision algorithm and provide cost analysis when integrating our approach into diagnostic pathways for DVT. Our approach is estimated to generate a positive net monetary benefit at costs up to £72 to £175 per software-supported examination, assuming a willingness to pay of £20,000/QALY.
EndoBind detects endogenous protein-protein interactions in real time
Authors: Bill Anke , Espinola Sheryll , Guthy Daniel , Haling Jacob R. , Lanter Mylene , Lu Min , Marelli Anthony , Mendiola Angelica , Miraglia Loren , Taylor Brandon L. , Vargas Leonardo , Orth Anthony P. , King Frederick J.
Published: September 2021

We present two high-throughput compatible methods to detect the interaction of ectopically expressed (RT-Bind) or endogenously tagged (EndoBind) proteins of interest. Both approaches provide temporal evaluation of dimer formation over an extended duration. Using examples of the Nrf2-KEAP1 and the CRAF-KRAS-G12V interaction, we demonstrate that our method allows for the detection of signal for more than 2 days after substrate addition, allowing for continuous monitoring of endogenous protein-protein interactions in real time.