bluuebunny/crossref_metadata_2025 huggingface dataset:
An intronic transposon insertion associates with a trans-species color polymorphism in Midas cichlid fishes
Authors: Kratochwil Claudius F. , Kautt Andreas F. , Nater Alexander , Härer Andreas , Liang Yipeng , Henning Frederico , Meyer Axel
Published: January 2022

Polymorphisms have fascinated biologists for a long time, but their genetic underpinnings often remain elusive. Here, we aim to uncover the genetic basis of the gold/dark polymorphism that is eponymous of Midas cichlid fish (Amphilophus spp.) adaptive radiations in Nicaraguan crater lakes. While most Midas cichlids are of the melanic “dark morph”, about 10% of individuals lose their melanic pigmentation during their ontogeny and transition into a conspicuous “gold morph”. Using a new haplotype-resolved long-read assembly we discover an 8.2 kb, transposon-derived inverted repeat in an intron of an undescribed gene, which we term goldentouch in reference to the Greek myth of King Midas. The gene goldentouch is differentially expressed between morphs, presumably due to structural implications of inverted repeats in both DNA and/or RNA (cruciform and hairpin formation). The near-perfect association of the insertion with the phenotype across independent populations suggests that it likely underlies this trans-specific, stable polymorphism.
Decarbonising the iron and steel sector for a 2 °C target using inherent waste streams
Authors: Sun Yongqi , Tian Sicong , Ciais Philippe , Zeng Zhenzhong , Meng Jing , Zhang Zuotai
Published: January 2022

The decarbonisation of the iron and steel industry, contributing approximately 8% of current global anthropogenic CO2 emissions, is challenged by the persistently growing global steel demand and limitations of techno-economically feasible options for low-carbon steelmaking. Here we explore the inherent potential of recovering energy and re-using materials from waste streams, high-temperature slag, and re-investing the revenues for carbon capture and storage. In a pathway based on energy recovery and resource recycling of glassy blast furnace slag and crystalline steel slag, we show that a reduction of 28.5 ± 5.7% CO2 emissions to the sectoral 2 °C target requirements in the iron and steel industry could be realized in 2050 under strong decarbonization policy consistent with low warming targets. The technological schemes applied to engineer this high-potential pathway could generate a revenue of US$35 ± 16 and US$40 ± 18 billion globally in 2035 and 2050, respectively. If this revenue is used for carbon capture and storage implementation, equivalent CO2 emission to the 2 °C sectoral target requirements is expected to be reduced before 2050, without any external investments.
Emergent Sasaki-Einstein geometry and AdS/CFT
Authors: Berman Robert J. , Collins Tristan C. , Persson Daniel
Published: January 2022

A central problem in any quantum theory of gravity is to explain the emergence of the classical spacetime geometry in some limit of a more fundamental, microscopic description of nature. The gauge/gravity-correspondence provides a framework in which this problem can, in principle, be addressed. This is a holographic correspondence which relates a supergravity theory in five-dimensional Anti-deSitter space to a strongly coupled superconformal gauge theory on its 4-dimensional flat Minkowski boundary. In particular, the classical geometry should therefore emerge from some quantum state of the dual gauge theory. Here we confirm this by showing how the classical metric emerges from a canonical state in the dual gauge theory. In particular, we obtain approximations to the Sasaki-Einstein metric underlying the supergravity geometry, in terms of an explicit integral formula involving the canonical quantum state in question. In the special case of toric quiver gauge theories we show that our results can be computationally simplified through a process of tropicalization.
Nuclear and mitochondrial DNA editing in human cells with zinc finger deaminases
Authors: Lim Kayeong , Cho Sung-Ik , Kim Jin-Soo
Published: January 2022

Base editing in nuclear DNA and mitochondrial DNA (mtDNA) is broadly useful for biomedical research, medicine, and biotechnology. Here, we present a base editing platform, termed zinc finger deaminases (ZFDs), composed of custom-designed zinc-finger DNA-binding proteins, the split interbacterial toxin deaminase DddAtox, and a uracil glycosylase inhibitor (UGI), which catalyze targeted C-to-T base conversions without inducing unwanted small insertions and deletions (indels) in human cells. We assemble plasmids encoding ZFDs using publicly available zinc finger resources to achieve base editing at frequencies of up to 60% in nuclear DNA and 30% in mtDNA. Because ZFDs, unlike CRISPR-derived base editors, do not cleave DNA to yield single- or double-strand breaks, no unwanted indels caused by error-prone non-homologous end joining are produced at target sites. Furthermore, recombinant ZFD proteins, expressed in and purified from E. coli, penetrate cultured human cells spontaneously to induce targeted base conversions, demonstrating the proof-of-principle of gene-free gene therapy.
4polar-STORM polarized super-resolution imaging of actin filament organization in cells
Authors: Rimoli Caio Vaz , Valades-Cruz Cesar Augusto , Curcio Valentina , Mavrakis Manos , Brasselet Sophie
Published: January 2022

Single-molecule localization microscopy provides insights into the nanometer-scale spatial organization of proteins in cells, however it does not provide information on their conformation and orientation, which are key functional signatures. Detecting single molecules’ orientation in addition to their localization in cells is still a challenging task, in particular in dense cell samples. Here, we present a polarization-splitting scheme which combines Stochastic Optical Reconstruction Microscopy (STORM) with single molecule 2D orientation and wobbling measurements, without requiring a strong deformation of the imaged point spread function. This method called 4polar-STORM allows, thanks to a control of its detection numerical aperture, to determine both single molecules’ localization and orientation in 2D and to infer their 3D orientation. 4polar-STORM is compatible with relatively high densities of diffraction-limited spots in an image, and is thus ideally placed for the investigation of dense protein assemblies in cells. We demonstrate the potential of this method in dense actin filament organizations driving cell adhesion and motility.
Molecular mechanism of agonism and inverse agonism in ghrelin receptor
Authors: Qin Jiao , Cai Ye , Xu Zheng , Ming Qianqian , Ji Su-Yu , Wu Chao , Zhang Huibing , Mao Chunyou , Shen Dan-Dan , Hirata Kunio , Ma Yanbin , Yan Wei , Zhang Yan , Shao Zhenhua
Published: January 2022

Much effort has been invested in the investigation of the structural basis of G protein-coupled receptors (GPCRs) activation. Inverse agonists, which can inhibit GPCRs with constitutive activity, are considered useful therapeutic agents, but the molecular mechanism of such ligands remains insufficiently understood. Here, we report a crystal structure of the ghrelin receptor bound to the inverse agonist PF-05190457 and a cryo-electron microscopy structure of the active ghrelin receptor-Go complex bound to the endogenous agonist ghrelin. Our structures reveal a distinct binding mode of the inverse agonist PF-05190457 in the ghrelin receptor, different from the binding mode of agonists and neutral antagonists. Combining the structural comparisons and cellular function assays, we find that a polar network and a notable hydrophobic cluster are required for receptor activation and constitutive activity. Together, our study provides insights into the detailed mechanism of ghrelin receptor binding to agonists and inverse agonists, and paves the way to design specific ligands targeting ghrelin receptors.
Algorithm-aided engineering of aliphatic halogenase WelO5* for the asymmetric late-stage functionalization of soraphens
Authors: Büchler Johannes , Malca Sumire Honda , Patsch David , Voss Moritz , Turner Nicholas J. , Bornscheuer Uwe T. , Allemann Oliver , Le Chapelain Camille , Lumbroso Alexandre , Loiseleur Olivier , Buller Rebecca
Published: January 2022

Late-stage functionalization of natural products offers an elegant route to create novel entities in a relevant biological target space. In this context, enzymes capable of halogenating sp3carbons with high stereo- and regiocontrol under benign conditions have attracted particular attention. Enabled by a combination of smart library design and machine learning, we engineer the iron/α-ketoglutarate dependent halogenase WelO5* for the late-stage functionalization of the complex and chemically difficult to derivatize macrolides soraphen A and C, potent anti-fungal agents. While the wild type enzyme WelO5* does not accept the macrolide substrates, our engineering strategy leads to active halogenase variants and improves upon their apparentkcatand total turnover number by more than 90-fold and 300-fold, respectively. Notably, our machine-learning guided engineering approach is capable of predicting more active variants and allows us to switch the regio-selectivity of the halogenases facilitating the targeted analysis of the derivatized macrolides’ structure-function activity in biological assays.
Stiffness control in dual color tomographic volumetric 3D printing
Authors: Wang Bin , Engay Einstom , Stubbe Peter R. , Moghaddam Saeed Z. , Thormann Esben , Almdal Kristoffer , Islam Aminul , Yang Yi
Published: January 2022

Tomographic volumetric printing (TVP) physically reverses tomography to offer fast and auxiliary-free 3D printing. Here we show that wavelength-sensitive photoresins can be cured using visible ($$\bar{\lambda }=455$$

λ

¯

=
455
 nm) and UV ($$\bar{\lambda }=365$$

λ

¯

=
365
 nm) sources simultaneously in a TVP setup to generate internal mechanical property gradients with high precision. We develop solutions of mixed acrylate and epoxy monomers and utilize the orthogonal chemistry between free radical and cationic polymerization to realize fully 3D stiffness control. The radial resolution of stiffness control is 300 µm or better and an average modulus gradient of 5 MPa/µm is achieved. We further show that the reactive transport of radical inhibitors defines a workpiece’s shape and limits the achievable stiffness contrast to a range from 127 MPa to 201 MPa according to standard tensile tests after post-processing. Our result presents a strategy for controlling the stiffness of material spatially in light-based volumetric additive manufacturing.
Optical fibre taper-enabled waveguide photoactuators
Authors: Xiao Jianliang , Zhou Tao , Yao Ni , Ma Shuqi , Pan Chenxinyu , Wang Pan , Fu Haoran , Liu Haitao , Pan Jing , Yu Longteng , Wang Shipeng , Yang Wenzhen , Tong Limin , Zhang Lei
Published: January 2022

Photoactuators have attracted significant interest for soft robot and gripper applications, yet most of them rely on free-space illumination, which requires a line-of-site low-loss optical path. While waveguide photoactuators can overcome this limitation, their actuating performances are fundamentally restricted by the nature of standard optical fibres. Herein, we demonstrated miniature photoactuators by embedding optical fibre taper in a polydimethylsiloxane/Au nanorod-graphene oxide photothermal film. The special geometric features of the taper endow the designed photoactuator with microscale active layer thickness, high energy density and optical coupling efficiency. Hence, our photoactuator show large bending angles (>270°), fast response (1.8 s for 180° bending), and low energy consumption (<0.55 mW/°), significantly exceeding the performance of state-of-the-art waveguide photoactuators. As a proof-of-concept study, one-arm and two-arm photoactuator-based soft grippers are demonstrated for capturing/moving small objects, which is challenging for free-space light-driven photoactuators.
C/EBPβ isoform-specific regulation of migration and invasion in triple-negative breast cancer cells
Authors: Sterken Britt A. , Ackermann Tobias , Müller Christine , Zuidhof Hidde R. , Kortman Gertrud , Hernandez-Segura Alejandra , Broekhuis Mathilde , Spierings Diana , Guryev Victor , Calkhoven Cornelis F.
Published: January 2022

The transcription factor C/EBPβ is a master regulator of mammary gland development and tissue remodelling during lactation. TheCEBPB-mRNA is translated into three distinct protein isoforms named C/EBPβ-LAP1, -LAP2 and -LIP that are functionally different. The smaller isoform LIP lacks the N-terminal transactivation domains and is considered to act as an inhibitor of the transactivating LAP1/2 isoforms by competitive binding for the same DNA recognition sequences. Aberrantly high expression of LIP is associated with mammary epithelial proliferation and is found in grade III, estrogen receptor (ER) and progesterone (PR) receptor-negative human breast cancer. Here, we show that reverting the high LIP/LAP ratios in triple-negative breast cancer (TNBC) cell lines into low LIP/LAP ratios by overexpression of LAP reduces migration and matrix invasion of these TNBC cells. In addition, in untransformed MCF10A human mammary epithelial cells overexpression of LIP stimulates migration. Knockout ofCEBPBin TNBC cells where LIP expression prevails, resulted in strongly reduced migration that was accompanied by a downregulation of genes involved in cell migration, extracellular matrix production and cytoskeletal remodelling, many of which are epithelial to mesenchymal transition (EMT) marker genes. Together, this study suggests that the LIP/LAP ratio is involved in regulating breast cancer cell migration and invasion. This study together with studies from others shows that understanding the functions the C/EBPβ-isoforms in breast cancer development may reveal new avenues of treatment.
HBXIP induces anoikis resistance by forming a reciprocal feedback loop with Nrf2 to maintain redox homeostasis and stabilize Prdx1 in breast cancer
Authors: Zhou Xiaolei , Li Li , Guo Xin , Zhang Chunxiao , Du Yanyan , Li Tianming , Tong Kaiqing , Zhu Chongyue , Wang Zijin
Published: January 2022

Anoikis resistance is an essential prerequisite for tumor metastasis, but the underlying molecular mechanisms remain unknown. Herein, we report that the oncoprotein hepatitis B X-interacting protein (HBXIP) is prominently upregulated in breast cancer cells following ECM detachment. Altering HBXIP expression can impair the anchorage-independent growth ability of tumor cells. Mechanistically, HBXIP, which binds to Kelch-like ECH-associated protein 1 (Keap1) to activate nuclear factor E2-related factor 2 (Nrf2), contains a cis-acting antioxidant response element (ARE) in the gene promoter and is a target gene of Nrf2. The HBXIP/Nrf2 axis forms a reciprocal positive feedback loop that reinforces the expression and tumor-promoting actions of each protein. In response to ECM detachment, Nrf2 reduces reactive oxygen species (ROS) accumulation, protects the mitochondrial membrane potential and increases cellular ATP, GSH and NADPH levels to maintain breast cancer cell survival. Meanwhile, the reinforcement of HBXIP induced by Nrf2 inhibits JNK1 activation by inhibiting ubiquitin-mediated degradation of Prdx1, which also plays an essential role in promoting ECM-detached cell survival. Furthermore, a strong positive correlation was identified between HBXIP expression and Prdx1 expression in clinical breast cancer tissues and TCGA Pan-Cancer Atlas clinical data of breast invasive carcinoma based on the cBioPortal cancer genomics database. Co-expression of HBXIP and Prdx1 predicts a poor prognosis for breast cancer patients. Collectively, our findings reveal a significant mechanism by which the HBXIP/Nrf2 feedback loop contributes to anoikis resistance by maintaining redox homeostasis and inhibiting JNK1 activation and support the likely therapeutic value of the HBXIP/Nrf2 axis in breast cancer patients.
Relativistic domain-wall dynamics in van der Waals antiferromagnet MnPS3
Authors: Alliati Ignacio M. , Evans Richard F. L. , Novoselov Kostya S. , Santos Elton J. G.
Published: January 2022

The discovery of two-dimensional (2D) magnetic van der Waals (vdW) materials has flourished an endeavor for fundamental problems as well as potential applications in computing, sensing and storage technologies. Of particular interest are antiferromagnets, which due to their intrinsic exchange coupling show several advantages in relation to ferromagnets such as robustness against external magnetic perturbations. Here we show that, despite of this cornerstone, the magnetic domains of recently discovered 2D vdW MnPS3 antiferromagnet can be controlled via magnetic fields and electric currents. We achieve ultrafast domain-wall dynamics with velocities up to ~3000 m s−1 within a relativistic kinematic. Lorentz contraction and emission of spin-waves in the terahertz gap are observed with dependence on the edge termination of the layers. Our results indicate that the implementation of 2D antiferromagnets in real applications can be further controlled through edge engineering which sets functional characteristics for ultrathin device platforms with relativistic features.
Cross-condition and cross-platform remaining useful life estimation via adversarial-based domain adaptation
Authors: Zhao Dongdong , Liu Feng
Published: January 2022

Supervised machine learning is a traditionally remaining useful life (RUL) estimation tool, which requires a lot of prior knowledge. For the situation lacking labeled data, supervised methods are invalid for the issue of domain shift in data distribution. In this paper, a adversarial-based domain adaptation (ADA) architecture with convolution neural networks (CNN) for RUL estimation of bearings under different conditions and platforms, referred to as ADACNN, is proposed. Specifically, ADACNN is trained in source labeled data and fine-tunes to similar target unlabeled data via an adversarial training and parameters shared mechanism. Besides a feature extractor and source domain regressive predictor, ADACNN also includes a domain classifier that tries to guide feature extractor find some domain-invariant features, which differents with traditional methods and belongs to a unsupervised learning in target domain, which has potential application value and far-reaching significance in academia. In addition, according to different first predictive time (FPT) detection mechanisms, we also explores the impact of different FPT detection mechanisms on RUL estimation performance. Finally, according to extensive experiments, the results of RUL estimation of bearing in cross-condition and cross-platform prove that ADACNN architecture has satisfactory generalization performance and great practical value in industry.
Plasmodium falciparum genomic surveillance reveals spatial and temporal trends, association of genetic and physical distance, and household clustering
Authors: Sy Mouhamad , Deme Awa B. , Warren Joshua L. , Early Angela , Schaffner Stephen , Daniels Rachel F. , Dieye Baba , Ndiaye Ibrahima Mbaye , Diedhiou Younous , Mbaye Amadou Moctar , Volkman Sarah K. , Hartl Daniel L. , Wirth Dyann F. , Ndiaye Daouda , Bei Amy K.
Published: January 2022

Molecular epidemiology using genomic data can help identify relationships between malaria parasite population structure, malaria transmission intensity, and ultimately help generate actionable data to assess the effectiveness of malaria control strategies. Genomic data, coupled with geographic information systems data, can further identify clusters or hotspots of malaria transmission, parasite genetic and spatial connectivity, and parasite movement by human or mosquito mobility over time and space. In this study, we performed longitudinal genomic surveillance in a cohort of 70 participants over four years from different neighborhoods and households in Thiès, Senegal—a region of exceptionally low malaria transmission (entomological inoculation rate less than 1). Genetic identity (identity by state, IBS) was established using a 24-single nucleotide polymorphism molecular barcode, identity by descent was calculated from whole genome sequence data, and a hierarchical Bayesian regression model was used to establish genetic and spatial relationships. Our results show clustering of genetically similar parasites within households and a decline in genetic similarity of parasites with increasing distance. One household showed extremely high diversity and warrants further investigation as to the source of these diverse genetic types. This study illustrates the utility of genomic data with traditional epidemiological approaches for surveillance and detection of trends and patterns in malaria transmission not only by neighborhood but also by household. This approach can be implemented regionally and countrywide to strengthen and support malaria control and elimination efforts.
Early-stage spatial disease surveillance of novel SARS-CoV-2 variants of concern in Germany with crowdsourced data
Authors: Mitze Timo , Rode Johannes
Published: January 2022

The emergence and rapid spread of novel variants of concern (VOC) of the coronavirus 2 constitute a major challenge for spatial disease surveillance. We explore the possibility to use close to real-time crowdsourced data on reported VOC cases (mainly the Alpha variant) at the local area level in Germany. The aim is to use these data for early-stage estimates of the statistical association between VOC reporting and the overall COVID-19 epidemiological development. For the first weeks in 2021 after international importation of VOC to Germany, our findings point to significant increases of up to 35–40% in the 7-day incidence rate and the hospitalization rate in regions with confirmed VOC cases compared to those without such cases. This is in line with simultaneously produced international evidence. We evaluate the sensitivity of our estimates to sampling errors associated with the collection of crowdsourced data. Overall, we find no statistical evidence for an over- or underestimation of effects once we account for differences in data representativeness at the regional level. This points to the potential use of crowdsourced data for spatial disease surveillance, local outbreak monitoring and public health decisions if no other data on new virus developments are available.
Accurate determination of marker location within whole-brain microscopy images
Authors: Tyson Adam L. , Vélez-Fort Mateo , Rousseau Charly V. , Cossell Lee , Tsitoura Chryssanthi , Lenzi Stephen C. , Obenhaus Horst A. , Claudi Federico , Branco Tiago , Margrie Troy W.
Published: January 2022

High-resolution whole-brain microscopy provides a means for post hoc determination of the location of implanted devices and labelled cell populations that are necessary to interpret in vivo experiments designed to understand brain function. Here we have developed two plugins (brainreg and brainreg-segment) for the Python-based image viewer napari, to accurately map any object in a common coordinate space. We analysed the position of dye-labelled electrode tracks and two-photon imaged cell populations expressing fluorescent proteins. The precise location of probes and cells were physiologically interrogated and revealed accurate segmentation with near-cellular resolution.
Laser-induced thermal source for cold atoms
Authors: Hsu Chung Chuan , Larue Rémy , Kwong Chang Chi , Wilkowski David
Published: January 2022

We demonstrate a simple and compact approach to laser cool and trap atoms based on laser-induced thermal ablation (LITA) of a pure solid granule. A rapid thermalisation of the granule leads to a fast recovery of the ultra-high vacuum condition required for a long trapping lifetime of the cold gas. We give a proof-of-concept of the technique, performing a magneto-optical trap on the 461 nm $$^1S_0\rightarrow \,^1P_1$$

1

S
0

→

1

P
1

transition of strontium. We get up to 3.5 million of cold strontium-88 atoms with a trapping lifetime of more than 4 s. The lifetime is limited by the pressure of the strontium-free residual background vapour. We also implement an original configuration of permanent magnets to create the quadruple magnetic field of the magneto-optical trap. The LITA technique can be generalized to other atomic elements such as transition metals and lanthanide atoms, and shows a strong potential for applications in quantum technologies ranging from quantum computing to precision measurements such as outdoor inertial sensing.
Mutations affecting the N-terminal domains of SHANK3 point to different pathomechanisms in neurodevelopmental disorders
Authors: Woike Daniel , Wang Emily , Tibbe Debora , Hassani Nia Fatemeh , Failla Antonio Virgilio , Kibæk Maria , Overgård Tinett Martesen , Larsen Martin J. , Fagerberg Christina R. , Barsukov Igor , Kreienkamp Hans-Jürgen
Published: January 2022

Shank proteins are major scaffolds of the postsynaptic density of excitatory synapses. Mutations in SHANK genes are associated with autism and intellectual disability. The effects of missense mutations on Shank3 function, and therefore the pathomechanisms are unclear. Several missense mutations in SHANK3 affect the N-terminal region, consisting of the Shank/ProSAP N-terminal (SPN) domain and a set of Ankyrin (Ank) repeats. Here we identify a novel SHANK3 missense mutation (p.L270M) in the Ankyrin repeats in patients with an ADHD-like phenotype. We functionally analysed this and a series of other mutations, using biochemical and biophysical techniques. We observe two major effects: (1) a loss of binding to δ-catenin (e.g. in the p.L270M variant), and (2) interference with the intramolecular interaction between N-terminal SPN domain and the Ank repeats. This also interferes with binding to the α-subunit of the calcium-/calmodulin dependent kinase II (αCaMKII), and appears to be associated with a more severe neurodevelopmental pathology.
Harnessing Artificial Intelligence to assess the impact of nonpharmaceutical interventions on the second wave of the Coronavirus Disease 2019 pandemic across the world
Authors: Tao Sile , Bragazzi Nicola Luigi , Wu Jianhong , Mellado Bruce , Kong Jude Dzevela
Published: January 2022

In the present paper, we aimed to determine the influence of various non-pharmaceutical interventions (NPIs) enforced during the first wave of COVID-19 across countries on the spreading rate of COVID-19 during the second wave. For this purpose, we took into account national-level climatic, environmental, clinical, health, economic, pollution, social, and demographic factors. We estimated the growth of the first and second wave across countries by fitting a logistic model to daily-reported case numbers, up to the first and second epidemic peaks. We estimated the basic and effective (second wave) reproduction numbers across countries. Next, we used a random forest algorithm to study the association between the growth rate of the second wave and NPIs as well as pre-existing country-specific characteristics. Lastly, we compared the growth rate of the first and second waves of COVID-19. The top three factors associated with the growth of the second wave were body mass index, the number of days that the government sets restrictions on requiring facial coverings outside the home at all times, and restrictions on gatherings of 10 people or less. Artificial intelligence techniques can help scholars as well as decision and policy-makers estimate the effectiveness of public health policies, and implement “smart” interventions, which are as efficacious as stringent ones.
Responsiveness of PNPLA3 and lipid-related transcription factors is dependent upon fatty acid profile in primary bovine hepatocytes
Authors: Erb Sophia J. , Chandler Tawny L. , White Heather M.
Published: January 2022

Knockdown of patatin-like phospholipase domain-containing protein 3 (PNPLA3) increased triglycerides (TG) in primary bovine hepatocytes, suggesting that PNPLA3 plays a causal role in hepatic TG clearing. In vivo, PNPLA3 abundance across the periparturient period is inversely related to hepatic TG accumulation and circulating fatty acid (FA) concentrations. The purpose of this research was to determine if PNPLA3, as well as other lipases, transcription factors, or FA-mediated genes, are regulated by FA mimicking liver lipid accumulation (ACCUM) and liver lipid clearing (RECOV) or singular FA physiologically found in dairy cows at 0.5 mM of circulating RECOV (iRECOV). Abundance of PNPLA3 tended to decrease with ACCUM and increased quadratically with RECOV (P ≤ 0.10), differing from PNPLA3 expression, but consistent with previous in vivo research. Adipose TG lipase abundance, but not other lipase abundances, was quadratically responsive to both ACCUM and RECOV (P ≤ 0.005). Abundance of PNPLA3 and SREBP1c and expression of LXRA responded similarly to iRECOV, with C18:0 tending to decrease abundance (P ≤ 0.07). Results indicate that bovine PNPLA3 is translationally regulated by FA and although a LXRA-SREBP1c pathway mediation is possible, the mechanism warrants further investigation.
Physical simulation study on grouting water plugging of flexible isolation layer in coal seam mining
Authors: Li Ang , Ji Bingnan , Ma Qiang , Ji Yadong , Mu Qian , Zhang Wenzhong , Mu Pengfei , Li Liang , Zhao Chunhu
Published: January 2022

Deep coal seam mining often leads to water resource loss due to bedrock water entering the workings of the mine and is discharged adjacent to the mining area. Using the geological conditions of the Maiduoshan coal mine, this paper applied a physical simulation experiment. The specified rock above the coal seam was hydraulically fractured in advance to form a postmining grouted fracture network, followed by grouting to construct a flexible isolation layer that blocked the infiltration of groundwater from the aquifer into the water-conducting fracture zone. Stress sensors, flow sensors and strata displacement monitoring technology were deployed inside the experimental material to study the spatial distribution characteristics and evolution law of the water-conducting fracture zone in the overlying rocks. Analysis of the water-conducting fracture zone development law, stress variation, overburden evolution characteristics, fracturing and grouting sequence of the flexible isolation layer and the effect of postmining grouting on the water barrier was conducted. These experiments verified the feasibility of fracture and grouting of the flexible isolation layer. These research results will provide practical guidance for the transition from the current safe and efficient mining methods to safe and green mining methods of deep coal mining in the western mining areas of China.
Novel regulation mechanism of adrenal cortisol and DHEA biosynthesis via the endogen ERAD inhibitor small VCP-interacting protein
Authors: Ilhan Recep , Üner Göklem , Yilmaz Sinem , Atalay Sahar Esra , Cayli Sevil , Erzurumlu Yalcin , Gozen Oguz , Ballar Kirmizibayrak Petek
Published: January 2022

Endoplasmic reticulum-associated degradation (ERAD) is a well-characterized mechanism of protein quality control by removal of misfolded or unfolded proteins. The tight regulation of ERAD is critical for protein homeostasis as well as lipid metabolism. Although the mechanism is complex, all ERAD branches converge on p97/VCP, a key protein in the retrotranslocation step. The multifunctionality of p97/VCP relies on its multiple binding partners, one of which is the endogenous ERAD inhibitor, SVIP (small VCP-interacting protein). As SVIP is a promising target for the regulation of ERAD, we aimed to assess its novel physiological roles. We revealed that SVIP is highly expressed in the rat adrenal gland, especially in the cortex region, at a consistently high level during postnatal development, unlike the gradual increase in expression seen in developing nerves. Steroidogenic stimulators caused a decrease in SVIP mRNA expression and increase in SVIP protein degradation in human adrenocortical H295R cells. Interestingly, silencing of SVIP diminished cortisol secretion along with downregulation of steroidogenic enzymes and proteins involved in cholesterol uptake and cholesterol biosynthesis. A certain degree of SVIP overexpression mainly increased the biosynthesis of cortisol as well as DHEA by enhancing the expression of key steroidogenic proteins, whereas exaggerated overexpression led to apoptosis, phosphorylation of eIF2α, and diminished adrenal steroid hormone biosynthesis. In conclusion, SVIP is a novel regulator of adrenal cortisol and DHEA biosynthesis, suggesting that alterations in SVIP expression levels may be involved in the deregulation of steroidogenic stimulator signaling and abnormal adrenal hormone secretion.
Accumulation and ecotoxicological risk assessment of heavy metals in surface sediments of the Olt River, Romania
Authors: Iordache Andreea Maria , Nechita Constantin , Zgavarogea Ramona , Voica Cezara , Varlam Mihai , Ionete Roxana Elena
Published: January 2022

Heavy metal pollution of river freshwater environments currently raises significant concerns due to the toxic effects and the fact that heavy metal behavior is not fully understood. This study assessed the contamination level of eight heavy metals and trace elements (Cr, Ni, Cu, Zn, As, Pb, Cd, and Hg) in the surface sediments of 19 sites in 2018 during four periods (March, May, June, and October) in Olt River sediments. Multivariate statistical techniques were used, namely, one-way ANOVA, person product-moment correlation analysis, principal component analysis, hierarchical cluster analysis, and sediment quality indicators such as the contamination factor and pollution load index. The results demonstrated higher contents of Ni, Cu, Zn, As, Pb, Cd, and Hg, with values that were over 2.46, 4.40, 1.15, 8.28, 1.10, 1.53, and 3.71 times more, respectively, compared with the national quality standards for sediments. We observed a positive significant statistical correlation (p < 0.001) in March between elevation and Pb, Ni, Cu, Cr, and Zn and a negative correlation between Pb and elevation (p = 0.08). Intermetal associations were observed only in March, indicating a relationship with river discharge from spring. The PCA sustained mainly anthropogenic sources of heavy metals, which were also identified through correlation and cluster analyses. We noted significant differences between the Cr and Pb population means and variances (p < 0.001) for the data measured in March, May, June, and October. The contamination factor indicated that the pollution level of heavy metals was high and significant for As at 15 of the 19 sites. The pollution load index showed that over 89% of the sites were polluted by metals to various degrees during the four periods investigated. Our results improve the knowledge of anthropogenic versus natural origins of heavy metals in river surface sediments, which is extremely important in assessing environmental and human health risks and beneficial for decision-maker outcomes for national freshwater management plans.
Identification of a fall armyworm (Spodoptera frugiperda)-specific gene and development of a rapid and sensitive loop-mediated isothermal amplification assay
Authors: Osabutey Angelina F. , Seo Bo Yoon , Kim A-Young , Ha Thu Anh Thi , Jung JinKyo , Goergen Georg , Owusu Ebenezer Oduro , Lee Gwan-Seok , Koh Young Ho
Published: January 2022

The fall armyworm [FAW, Spodoptera frugiperda (J E Smith)], a moth native to America, has spread throughout the world since it was first discovered in Africa in 2016. The FAW is a polyphagous migratory pest that can travel over long distances using seasonal winds or typhoons because of its excellent flying ability, causing serious damage to many crops. For effective FAW control, accurate species identification is essential at the beginning of the invasion. In this study, the FAW-specific gene Sf00067 was discovered by performing bioinformatics to develop a fast and accurate tool for the species-specific diagnosis of this pest. An Sf00067 loop-mediated isothermal amplification (LAMP) assay was developed, and optimal conditions were established. The Sf00067 6 primer LAMP (Sf6p-LAMP) assay established in this study was able to diagnose various genotype-based strains of FAW captured in Korea and FAWs collected from Benin, Africa. Our FAW diagnostic protocol can be completed within 30 min, from the process of extracting genomic DNA from an egg or a 1st instar larva to species determination.
brca2-mutant zebrafish exhibit context- and tissue-dependent alterations in cell phenotypes and response to injury
Authors: Kouprianov Vassili A. , Selmek Aubrie A. , Ferguson Jordan L. , Mo Xiaokui , Shive Heather R.
Published: January 2022

Cancer cells frequently co-opt molecular programs that are normally activated in specific contexts, such as embryonic development and the response to injury. Determining the impact of cancer-associated mutations on cellular phenotypes within these discrete contexts can provide new insight into how such mutations lead to dysregulated cell behaviors and subsequent cancer onset. Here we assess the impact of heritable BRCA2 mutation on embryonic development and the injury response using a zebrafish model (Danio rerio). Unlike most mouse models for BRCA2 mutation, brca2-mutant zebrafish are fully viable and thus provide a unique tool for assessing both embryonic and adult phenotypes. We find that maternally provided brca2 is critical for normal oocyte development and embryonic survival in zebrafish, suggesting that embryonic lethality associated with BRCA2 mutation is likely to reflect defects in both meiotic and embryonic developmental programs. On the other hand, we find that adult brca2-mutant zebrafish exhibit aberrant proliferation of several cell types under basal conditions and in response to injury in tissues at high risk for cancer development. These divergent effects exemplify the often-paradoxical outcomes that occur in embryos (embryonic lethality) versus adult animals (cancer predisposition) with mutations in cancer susceptibility genes such as BRCA2. The altered cell behaviors identified in brca2-mutant embryonic and adult tissues, particularly in adult tissues at high risk for cancer, indicate that the effects of BRCA2 mutation on cellular phenotypes are both context- and tissue-dependent.
Technical field measurements of muscular workload during stocking activities in supermarkets: cross-sectional study
Authors: Skovlund Sebastian Venge , Bláfoss Rúni , Skals Sebastian , Jakobsen Markus Due , Andersen Lars Louis
Published: January 2022

Multiple studies have reported high prevalence of musculoskeletal disorders among supermarket workers. Technical field measurements can provide important knowledge about ergonomic risk factors for musculoskeletal disorders in the physical working environment, but these measurements are lacking in the supermarket sector. Therefore, using wearable electromyography and synchronous video recording in 75 supermarket workers, this cross-sectional study measured muscular workload during stocking activities in six different types of general store departments and during the thirteen most common work tasks across five different supermarket chains. Our results showed that muscular workload varies, especially for the low-back muscles, across (1) supermarket chains, (2) departments, and (3) specific stocking activities. Highest workloads of the low-back and neck/shoulders were seen in the fruit and vegetables department and during heavy, two-handed lifts of parcels (especially without using technical aids). In conclusion, physical work demands during supermarket stocking activities differ between chains, departments, and work tasks. These results can be used by company representatives and work environment professionals to specifically address and organize the stocking procedures to reduce the muscular workload during supermarket stocking.
Pathology and virology of natural highly pathogenic avian influenza H5N8 infection in wild Common buzzards (Buteo buteo)
Authors: Caliendo Valentina , Leijten Lonneke , van de Bildt Marco W. G. , Fouchier Ron A. M. , Rijks Jolianne M. , Kuiken Thijs
Published: January 2022

Highly pathogenic avian influenza (HPAI) in wild birds is a major emerging disease, and a cause of increased mortality during outbreaks. The Common buzzard (Buteo buteo) has a considerable chance of acquiring the infection and therefore may function as bio-sentinel for the presence of virus in wildlife. This study aimed to determine the virus distribution and associated pathological changes in the tissues of Common buzzards that died with HPAI H5 virus infection during the 2020–2021 epizootic. Eleven freshly dead, HPAI H5 virus-positive Common buzzards were necropsied. Based on RT-PCR, all birds were systemically infected with HPAI H5N8 virus, as viral RNA was detected in cloacal and pharyngeal swabs and in all 10 selected tissues of the birds, with mean Ct values per tissue ranging from 22 for heart to 32 for jejunum. Based on histology and immunohistochemistry, the most common virus-associated pathological changes were necrotizing encephalitis (9/11 birds) and necrotizing myocarditis (7/11 birds). The proventriculus of two birds showed virus-associated necrosis, indicating tropism of this virus for the digestive tract. Our advice is to collect at least a miniset of samples including brain, heart, liver, and spleen, as these tissues were positive both by RT-PCR and for virus-antigen-associated lesions.
Cycloidal CT with CNN-based sinogram completion and in-scan generation of training data
Authors: Pelt Daniël M. , Roche i Morgó Oriol , Maughan Jones Charlotte , Olivo Alessandro , Hagen Charlotte K.
Published: January 2022

In x-ray computed tomography (CT), the achievable image resolution is typically limited by several pre-fixed characteristics of the x-ray source and detector. Structuring the x-ray beam using a mask with alternating opaque and transmitting septa can overcome this limit. However, the use of a mask imposes an undersampling problem: to obtain complete datasets, significant lateral sample stepping is needed in addition to the sample rotation, resulting in high x-ray doses and long acquisition times. Cycloidal CT, an alternative scanning scheme by which the sample is rotated and translated simultaneously, can provide high aperture-driven resolution without sample stepping, resulting in a lower radiation dose and faster scans. However, cycloidal sinograms are incomplete and must be restored before tomographic images can be computed. In this work, we demonstrate that high-quality images can be reconstructed by applying the recently proposed Mixed Scale Dense (MS-D) convolutional neural network (CNN) to this task. We also propose a novel training approach by which training data are acquired as part of each scan, thus removing the need for large sets of pre-existing reference data, the acquisition of which is often not practicable or possible. We present results for both simulated datasets and real-world data, showing that the combination of cycloidal CT and machine learning-based data recovery can lead to accurate high-resolution images at a limited dose.
Assay of honey freshness by a novel optical technique
Authors: Mashhadi Alireza , Bavali Ali , Mokhtari Farzad
Published: January 2022

Assay of Maillard reaction products (e.g. furosine) is a reputable method for determination of the honey freshness. In this report, novel optical technique is proposed for real-time measurement of the changes of furosine content in honey. The method is based on the unidirectional energy transfer between two peaks of the doubled-peak fluorescence spectrum as secondary inner filter effect (2nd-IFE) in a specific arrangement of the laser induced fluorescence (LIF) setup. Proper optical parameters are defined accordingly, and affirmed to be dependent on the content of furosine in honey. It is shown that the introduced parameters are not sensitive to the LIF intensity fluctuations induced by the ambient noises and particularly alter due to the 2nd-IFE. Furosine level of 8 honey types with different botanical origin were chemically determined before and after the 1 year storage, and compared with the values of the devised spectral parameters. Proofs conducted that the proposed technique can be utilized for evaluation of the honey freshness.
Novel pathway for the sonochemical synthesis of silver nanoparticles with near-spherical shape and high stability in aqueous media
Authors: Calderón-Jiménez Bryan , Montoro Bustos Antonio R. , Pereira Reyes Reinaldo , Paniagua Sergio A. , Vega-Baudrit José R.
Published: January 2022

The present study shows the development of a novel sonochemical synthesis pathway of sub-15 nm silver nanoparticles (AgNPs) with quasi-spherical shape and high stability in aqueous suspension. Different analytical techniques such as on-line UV–Vis spectroscopy, Atomic Force Microscopy (AFM), and Transmission Electron Microscopy (TEM) were complementarily used to characterize the evolution of the properties of AgNPs synthesized with this new route. Furthermore, different centrifugation conditions were studied to establish a practical, simple and straightforward purification method. Particle size was determined by TEM employing two different deposition methods, showing that purified AgNPs have a size of 8.1 nm ± 2.4 nm with a narrow dispersion of the size distribution (95% coverage interval from 3.4 to 13 nm). Critical information of the shape and crystalline structure of these sub-15 nm AgNPs, provided by shape descriptors (circularity and roundness) using TEM and high resolution (HR)-TEM measurements, confirmed the generation of AgNPs with quasi-spherical shapes with certain twin-fault particles promoted by the high energy of the ultrasonic treatment. Elemental analysis by TEM-EDS confirmed the high purity of the sub-15 nm AgNPs, consisting solely of Ag. At the optical level, these AgNPs showed a bandgap energy of (2.795 ± 0.002) eV. Finally, the evaluation of the effects of ultraviolet radiation (UVC: 254 nm and UVA: 365 nm) and storage temperature on the spectral stability revealed high stability of the optical properties and subsequently dimensional properties of sub-15 nm AgNPs in the short-term (600 min) and long-term (24 weeks).
The impact of security countermeasures on human behavior during active shooter incidents
Authors: Zhu Runhe , Lucas Gale M. , Becerik-Gerber Burcin , Southers Erroll G. , Landicho Earl
Published: January 2022

Active shooter incidents represent an increasing threat to American society, especially in commercial and educational buildings. In recent years, a wide variety of security countermeasures have been recommended by public and governmental agencies. Many of these countermeasures are aimed to increase building security, yet their impact on human behavior when an active shooter incident occurs remains underexplored. To fill this research gap, we conducted virtual experiments to evaluate the impact of countermeasures on human behavior during active shooter incidents. A total of 162 office workers and middle/high school teachers were recruited to respond to an active shooter incident in virtual office and school buildings with or without the implementation of multiple countermeasures. The experiment results showed countermeasures significantly influenced participants’ response time and decisions (e.g., run, hide, fight). Participants’ responses and perceptions of the active shooter incident were also contingent on their daily roles, as well as building and social contexts. Teachers had more concerns for occupants’ safety than office workers. Moreover, teachers had more positive perceptions of occupants in the school, whereas office workers had more positive perceptions of occupants in the office.