bluuebunny/crossref_metadata_2025 huggingface dataset:
The landscape of molecular chaperones across human tissues reveals a layered architecture of core and variable chaperones
Authors: Shemesh Netta , Jubran Juman , Dror Shiran , Simonovsky Eyal , Basha Omer , Argov Chanan , Hekselman Idan , Abu-Qarn Mehtap , Vinogradov Ekaterina , Mauer Omry , Tiago Tatiana , Carra Serena , Ben-Zvi Anat , Yeger-Lotem Esti
Published: April 2021

The sensitivity of the protein-folding environment to chaperone disruption can be highly tissue-specific. Yet, the organization of the chaperone system across physiological human tissues has received little attention. Through computational analyses of large-scale tissue transcriptomes, we unveil that the chaperone system is composed of core elements that are uniformly expressed across tissues, and variable elements that are differentially expressed to fit with tissue-specific requirements. We demonstrate via a proteomic analysis that the muscle-specific signature is functional and conserved. Core chaperones are significantly more abundant across tissues and more important for cell survival than variable chaperones. Together with variable chaperones, they form tissue-specific functional networks. Analysis of human organ development and aging brain transcriptomes reveals that these functional networks are established in development and decline with age. In this work, we expand the known functional organization of de novo versus stress-inducible eukaryotic chaperones into a layered core-variable architecture in multi-cellular organisms.
Two-dimensional TIRF-SIM–traction force microscopy (2D TIRF-SIM-TFM)
Authors: Barbieri Liliana , Colin-York Huw , Korobchevskaya Kseniya , Li Di , Wolfson Deanna L. , Karedla Narain , Schneider Falk , Ahluwalia Balpreet S. , Seternes Tore , Dalmo Roy A. , Dustin Michael L. , Li Dong , Fritzsche Marco
Published: April 2021

Quantifying small, rapidly evolving forces generated by cells is a major challenge for the understanding of biomechanics and mechanobiology in health and disease. Traction force microscopy remains one of the most broadly applied force probing technologies but typically restricts itself to slow events over seconds and micron-scale displacements. Here, we improve >2-fold spatially and >10-fold temporally the resolution of planar cellular force probing compared to its related conventional modalities by combining fast two-dimensional total internal reflection fluorescence super-resolution structured illumination microscopy and traction force microscopy. This live-cell 2D TIRF-SIM-TFM methodology offers a combination of spatio-temporal resolution enhancement relevant to forces on the nano- and sub-second scales, opening up new aspects of mechanobiology to analysis.
Go Get Data (GGD) is a framework that facilitates reproducible access to genomic data
Authors: Cormier Michael J. , Belyeu Jonathan R. , Pedersen Brent S. , Brown Joseph , Köster Johannes , Quinlan Aaron R.
Published: April 2021

The rapid increase in the amount of genomic data provides researchers with an opportunity to integrate diverse datasets and annotations when addressing a wide range of biological questions. However, genomic datasets are deposited on different platforms and are stored in numerous formats from multiple genome builds, which complicates the task of collecting, annotating, transforming, and integrating data as needed. Here, we developed Go Get Data (GGD) as a fast, reproducible approach to installing standardized data recipes. GGD is available on Github (https://gogetdata.github.io/), is extendable to other data types, and can streamline the complexities typically associated with data integration, saving researchers time and improving research reproducibility.
Regulation of Arabidopsis photoreceptor CRY2 by two distinct E3 ubiquitin ligases
Authors: Chen Yadi , Hu Xiaohua , Liu Siyuan , Su Tiantian , Huang Hsiaochi , Ren Huibo , Gao Zhensheng , Wang Xu , Lin Deshu , Wohlschlegel James A. , Wang Qin , Lin Chentao
Published: April 2021

Cryptochromes (CRYs) are photoreceptors or components of the molecular clock in various evolutionary lineages, and they are commonly regulated by polyubiquitination and proteolysis. Multiple E3 ubiquitin ligases regulate CRYs in animal models, and previous genetics study also suggest existence of multiple E3 ubiquitin ligases for plant CRYs. However, only one E3 ligase, Cul4COP1/SPAs, has been reported for plant CRYs so far. Here we show that Cul3LRBs is the second E3 ligase of CRY2 in Arabidopsis. We demonstrate the blue light-specific and CRY-dependent activity of LRBs (Light-Response Bric-a-Brack/Tramtrack/Broad 1, 2 & 3) in blue-light regulation of hypocotyl elongation. LRBs physically interact with photoexcited and phosphorylated CRY2, at the CCE domain of CRY2, to facilitate polyubiquitination and degradation of CRY2 in response to blue light. We propose that Cul4COP1/SPAs and Cul3LRBs E3 ligases interact with CRY2 via different structure elements to regulate the abundance of CRY2 photoreceptor under different light conditions, facilitating optimal photoresponses of plants grown in nature.
A generalized density-modulated twist-splay-bend phase of banana-shaped particles
Authors: Chiappini Massimiliano , Dijkstra Marjolein
Published: April 2021

In 1976, Meyer predicted that bend distortions of the nematic director field are complemented by deformations of either twist or splay, yielding twist-bend and splay-bend nematic phases, respectively. Four decades later, the existence of the splay-bend nematic phase remains dubious, and the origin of these spontaneous distortions uncertain. Here, we conjecture that bend deformations of the nematic director can be complemented by simultaneous distortions of both twist and splay, yielding a twist-splay-bend nematic phase. Using theory and simulations, we show that the coupling between polar order and bend deformations drives the formation of modulated phases in systems of curved rods. We find that twist-bend phases transition to splay-bend phases via intermediate twist-splay-bend phases, and that splay distortions are always accompanied by periodic density modulations due to the coupling of the particle curvature with the non-uniform curvature of the splayed director field, implying that the twist-splay-bend and splay-bend phases of banana-shaped particles are actually smectic phases.
Epigenetic modulation of immune synaptic-cytoskeletal networks potentiates γδ T cell-mediated cytotoxicity in lung cancer
Authors: Weng Rueyhung R. , Lu Hsuan-Hsuan , Lin Chien-Ting , Fan Chia-Chi , Lin Rong-Shan , Huang Tai-Chung , Lin Shu-Yung , Huang Yi-Jhen , Juan Yi-Hsiu , Wu Yi-Chieh , Hung Zheng-Ci , Liu Chi , Lin Xuan-Hui , Hsieh Wan-Chen , Chiu Tzu-Yuan , Liao Jung-Chi , Chiu Yen-Ling , Chen Shih-Yu , Yu Chong-Jen , Tsai Hsing-Chen
Published: April 2021

γδ T cells are a distinct subgroup of T cells that bridge the innate and adaptive immune system and can attack cancer cells in an MHC-unrestricted manner. Trials of adoptive γδ T cell transfer in solid tumors have had limited success. Here, we show that DNA methyltransferase inhibitors (DNMTis) upregulate surface molecules on cancer cells related to γδ T cell activation using quantitative surface proteomics. DNMTi treatment of human lung cancer potentiates tumor lysis by ex vivo-expanded Vδ1-enriched γδ T cells. Mechanistically, DNMTi enhances immune synapse formation and mediates cytoskeletal reorganization via coordinated alterations of DNA methylation and chromatin accessibility. Genetic depletion of adhesion molecules or pharmacological inhibition of actin polymerization abolishes the potentiating effect of DNMTi. Clinically, the DNMTi-associated cytoskeleton signature stratifies lung cancer patients prognostically. These results support a combinatorial strategy of DNMTis and γδ T cell-based immunotherapy in lung cancer management.
Fire-induced rock spalling as a mechanism of weathering responsible for flared slope and inselberg development
Authors: Buckman Solomon , Morris Rowena H. , Bourman Robert P.
Published: April 2021

Inselbergs, such as Uluru in central Australia, are iconic landscape features of semi-arid and deeply denuded continental interiors. These islands of rock are commonly skirted by steep, overhanging cliffs (flared slopes) at ground level. The weathering processes responsible for formation of flared slopes and steep-sided inselbergs in flat, planated landscapes are enigmatic. One model emphasizes sub-surface weathering followed by denudation and excavation of saprolite to expose the unweathered bedrock while other models advocate slope development under subaerial conditions at ground level. We present a new hypothesis that identifies wildfire as a primary agent of flared slope development via fire-induced rock spalling around the periphery of inselbergs. Widespread fire-spalling following the 2019–2020 Australian fires illustrates that this is a common form of physical weathering in fire-prone environments but its effects are particularly evident in semi-arid regions where lateral fire-spalling dominates over fluvial and chemical weathering to create flared slopes and steep-sided inselbergs.
Targeted apoptosis of macrophages and osteoclasts in arthritic joints is effective against advanced inflammatory arthritis
Authors: Deng Caifeng , Zhang Quan , He Penghui , Zhou Bin , He Ke , Sun Xun , Lei Guanghua , Gong Tao , Zhang Zhirong
Published: April 2021

Insufficient apoptosis of inflammatory macrophages and osteoclasts (OCs) in rheumatoid arthritis (RA) joints contributes toward the persistent progression of joint inflammation and destruction. Here, we deliver celastrol (CEL) to selectively induce apoptosis of OCs and macrophages in arthritic joints, with enzyme-responsive nanoparticles (termed PRNPs) composed of RGD modified nanoparticles (termed RNPs) covered with cleavable PEG chains. CEL-loaded PRNPs (CEL-PRNPs) dually target OCs and inflammatory macrophages derived from patients with RA via an RGD-αvβ3 integrin interaction after PEG cleavage by matrix metalloprotease 9, leading to increased apoptosis of these cells. In an adjuvant-induced arthritis rat model, PRNPs have an arthritic joint-specific distribution and CEL-PRNPs efficiently reduce the number of OCs and inflammatory macrophages within these joints. Additionally, rats with advanced arthritis go into inflammatory remission with bone erosion repair and negligible side effects after CEL-PRNPs treatment. These findings indicate potential for targeting chemotherapy-induced apoptosis in the treatment of advanced inflammatory arthritis.
Ultrafast light field tomography for snapshot transient and non-line-of-sight imaging
Authors: Feng Xiaohua , Gao Liang
Published: April 2021

Cameras with extreme speeds are enabling technologies in both fundamental and applied sciences. However, existing ultrafast cameras are incapable of coping with extended three-dimensional scenes and fall short for non-line-of-sight imaging, which requires a long sequence of time-resolved two-dimensional data. Current non-line-of-sight imagers, therefore, need to perform extensive scanning in the spatial and/or temporal dimension, restricting their use in imaging only static or slowly moving objects. To address these long-standing challenges, we present here ultrafast light field tomography (LIFT), a transient imaging strategy that offers a temporal sequence of over 1000 and enables highly efficient light field acquisition, allowing snapshot acquisition of the complete four-dimensional space and time. With LIFT, we demonstrated three-dimensional imaging of light in flight phenomena with a <10 picoseconds resolution and non-line-of-sight imaging at a 30 Hz video-rate. Furthermore, we showed how LIFT can benefit from deep learning for an improved and accelerated image formation. LIFT may facilitate broad adoption of time-resolved methods in various disciplines.
Autophagy of the m6A mRNA demethylase FTO is impaired by low-level arsenic exposure to promote tumorigenesis
Authors: Cui Yan-Hong , Yang Seungwon , Wei Jiangbo , Shea Christopher R. , Zhong Wen , Wang Fang , Shah Palak , Kibriya Muhammad G. , Cui Xiaolong , Ahsan Habibul , He Chuan , He Yu-Ying
Published: April 2021

Here we show that FTO as an N6-methyladenosine (m6A) RNA demethylase is degraded by selective autophagy, which is impaired by low-level arsenic exposure to promote tumorigenesis. We found that in arsenic-associated human skin lesions, FTO is upregulated, while m6A RNA methylation is downregulated. In keratinocytes, chronic relevant low-level arsenic exposure upregulated FTO, downregulated m6A RNA methylation, and induced malignant transformation and tumorigenesis. FTO deletion inhibited arsenic-induced tumorigenesis. Moreover, in mice, epidermis-specific FTO deletion prevented skin tumorigenesis induced by arsenic and UVB irradiation. Targeting FTO genetically or pharmacologically inhibits the tumorigenicity of arsenic-transformed tumor cells. We identified NEDD4L as the m6A-modified gene target of FTO. Finally, arsenic stabilizes FTO protein through inhibiting p62-mediated selective autophagy. FTO upregulation can in turn inhibit autophagy, leading to a positive feedback loop to maintain FTO accumulation. Our study reveals FTO-mediated dysregulation of mRNA m6A methylation as an epitranscriptomic mechanism to promote arsenic tumorigenicity.
Reciprocal regulation of RIG-I and XRCC4 connects DNA repair with RIG-I immune signaling
Authors: Guo Guijie , Gao Ming , Gao Xiaochen , Zhu Bibo , Huang Jinzhou , Tu Xinyi , Kim Wootae , Zhao Fei , Zhou Qin , Zhu Shouhai , Wu Zheming , Yan Yuanliang , Zhang Yong , Zeng Xiangyu , Zhu Qian , Yin Ping , Luo Kuntian , Sun Jie , Deng Min , Lou Zhenkun
Published: April 2021

The RNA-sensing pathway contributes to type I interferon (IFN) production induced by DNA damaging agents. However, the potential involvement of RNA sensors in DNA repair is unknown. Here, we found that retinoic acid-inducible gene I (RIG-I), a key cytosolic RNA sensor that recognizes RNA virus and initiates the MAVS-IRF3-type I IFN signaling cascade, is recruited to double-stranded breaks (DSBs) and suppresses non-homologous end joining (NHEJ). Mechanistically, RIG-I interacts with XRCC4, and the RIG-I/XRCC4 interaction impedes the formation of XRCC4/LIG4/XLF complex at DSBs. High expression of RIG-I compromises DNA repair and sensitizes cancer cells to irradiation treatment. In contrast, depletion of RIG-I renders cells resistant to irradiation in vitro and in vivo. In addition, this mechanism suggests a protective role of RIG-I in hindering retrovirus integration into the host genome by suppressing the NHEJ pathway. Reciprocally, XRCC4, while suppressed for its DNA repair function, has a critical role in RIG-I immune signaling through RIG-I interaction. XRCC4 promotes RIG-I signaling by enhancing oligomerization and ubiquitination of RIG-I, thereby suppressing RNA virus replication in host cells. In vivo, silencing XRCC4 in mouse lung promotes influenza virus replication in mice and these mice display faster body weight loss, poorer survival, and a greater degree of lung injury caused by influenza virus infection. This reciprocal regulation of RIG-I and XRCC4 reveals a new function of RIG-I in suppressing DNA repair and virus integration into the host genome, and meanwhile endues XRCC4 with a crucial role in potentiating innate immune response, thereby helping host to prevail in the battle against virus.
Uncovering transcriptional dark matter via gene annotation independent single-cell RNA sequencing analysis
Authors: Wang Michael F. Z. , Mantri Madhav , Chou Shao-Pei , Scuderi Gaetano J. , McKellar David W. , Butcher Jonathan T. , Danko Charles G. , De Vlaminck Iwijn
Published: April 2021

Conventional scRNA-seq expression analyses rely on the availability of a high quality genome annotation. Yet, as we show here with scRNA-seq experiments and analyses spanning human, mouse, chicken, mole rat, lemur and sea urchin, genome annotations are often incomplete, in particular for organisms that are not routinely studied. To overcome this hurdle, we created a scRNA-seq analysis routine that recovers biologically relevant transcriptional activity beyond the scope of the best available genome annotation by performing scRNA-seq analysis on any region in the genome for which transcriptional products are detected. Our tool generates a single-cell expression matrix for all transcriptionally active regions (TARs), performs single-cell TAR expression analysis to identify biologically significant TARs, and then annotates TARs using gene homology analysis. This procedure uses single-cell expression analyses as a filter to direct annotation efforts to biologically significant transcripts and thereby uncovers biology to which scRNA-seq would otherwise be in the dark.
Defect-free potassium manganese hexacyanoferrate cathode material for high-performance potassium-ion batteries
Authors: Deng Leqing , Qu Jiale , Niu Xiaogang , Liu Juzhe , Zhang Juan , Hong Youran , Feng Meiying , Wang Jiangwei , Hu Miao , Zeng Liang , Zhang Qianfan , Guo Lin , Zhu Yujie
Published: April 2021

Potassium-ion batteries (KIBs) are promising electrochemical energy storage systems because of their low cost and high energy density. However, practical exploitation of KIBs is hampered by the lack of high-performance cathode materials. Here we report a potassium manganese hexacyanoferrate (K2Mn[Fe(CN)6]) material, with a negligible content of defects and water, for efficient high-voltage K-ion storage. When tested in combination with a K metal anode, the K2Mn[Fe(CN)6]-based electrode enables a cell specific energy of 609.7 Wh kg−1 and 80% capacity retention after 7800 cycles. Moreover, a K-ion full-cell consisting of graphite and K2Mn[Fe(CN)6] as anode and cathode active materials, respectively, demonstrates a specific energy of 331.5 Wh kg−1, remarkable rate capability, and negligible capacity decay for 300 cycles. The remarkable electrochemical energy storage performances of the K2Mn[Fe(CN)6] material are attributed to its stable frameworks that benefit from the defect-free structure.
Short-wave infrared organic phototransistors with strong infrared-absorbing polytriarylamine by electron-transfer doping
Authors: Lee Chulyeon , Kim Hwajeong , Kim Youngkyoo
Published: April 2021

Short-wavelength infrared (SWIR) sensors have attracted keen attention due to the increasing necessity in a variety of scientific and industrial applications, including biomedical and information technology fields. Because conventional SWIR sensors are made of inorganic materials with rigid and brittle characteristics, organic materials with a discrete SWIR absorption are required for flexible SWIR sensors in the flexible electronics era. Here, we demonstrate that a polytriarylamine, poly[N,N′-bis(4-butylphenyl)-N,N′-bis(phenyl)benzidine] (PolyTPD), can absorb almost full range of SWIR wavelength (λ = 1000–3200 nm) after 48 h doping with tris(pentafluorophenyl)borane (BCF). The spectroscopic characterization disclosed that an electron transfer from PolyTPD to BCF created a new low energy level (gap) state leading to the SWIR absorption in the BCF-doped PolyTPD complexes. Organic phototransistors (OPTRs) with the BCF-doped PolyTPD films as a gate-sensing layer could detect the SWIR light with a reasonable photoresponsivity of ~538 mA W−1 (λ = 1500 nm), ~541 mA W−1 (λ = 2000 nm), and ~222 mA W−1 (λ = 3000 nm). The present breakthrough SWIR-OPTR technology can pave a way for further advances in SWIR-absorbing organic materials and flexible SWIR sensors.
Initial atomic-scale oxidation pathways on a Ni–15Cr(100) alloy surface
Authors: Blades William H. , Barone Matthew R. , Reinke Petra
Published: April 2021

To understand the atomistic phenomenon behind initial oxidation processes, we have studied the nanoscale evolution of oxide growth prior to the formation of a complete layer on a Ni–15 wt%Cr(100) alloy surface using scanning tunneling microscopy/spectroscopy (STM/STS). At the onset of oxidation, a NiO superlattice forms oxide wedges across the step edges, eventually growing across the terraces. The completion of the NiO layer is followed by nucleation of the next layer, which always commences at the groove site of the superlattice. The Cr-oxide formation initiates as disk-shaped oxide particles early in the oxidation process, which Monte Carlo simulations reveal are likely caused by Cr clustering across the alloy surface. Upon further oxidation, a Cr(100)-p(2 × 2)O reconstructed surface is observed, indicating phase separation of Cr predicates the formation of the passive Cr-oxide film. The STS results vary across the oxide–alloy interface and between each oxide, providing greater insight into the origins of electronic heterogeneity and their effect on oxide growth. Using these data, we propose an oxidation model that highlights the growth of partial oxide layers on Ni–Cr(100) alloys within the pre-Cabrera–Mott regime.
Lower limb kinematic, kinetic, and EMG data from young healthy humans during walking at controlled speeds
Authors: Moreira Luís , Figueiredo Joana , Fonseca Pedro , Vilas-Boas João P. , Santos Cristina P.
Published: April 2021

Understanding the lower limb kinematic, kinetic, and electromyography (EMG) data interrelation in controlled speeds is challenging for fully assessing human locomotion conditions. This paper provides a complete dataset with the above-mentioned raw and processed data simultaneously recorded for sixteen healthy participants walking on a 10 meter-flat surface at seven controlled speeds (1.0, 1.5, 2.0, 2.5, 3.0, 3.5, and 4.0 km/h). The raw data include 3D joint trajectories of 24 retro-reflective markers, ground reaction forces (GRF), force plate moments, center of pressures, and EMG signals from Tibialis Anterior, Gastrocnemius Lateralis, Biceps Femoris, and Vastus Lateralis. The processed data present gait cycle-normalized data including filtered EMG signals and their envelope, 3D GRF, joint angles, and torques. This study details the experimental setup and presents a brief validation of the data quality. The presented dataset may contribute to (i) validate and enhance human biomechanical gait models, and (ii) serve as a reference trajectory for personalized control of robotic assistive devices, aiming an adequate assistance level adjusted to the gait speed and user’s anthropometry.
Central and mid-peripheral corneal astigmatism in an elderly population: a retrospective analysis of Scheimpflug topography results
Authors: Łabuz Grzegorz , Varadi Dorottya , Khoramnia Ramin , Auffarth Gerd U.
Published: April 2021

Implantation of toric intraocular lenses (IOLs) has become standard in the correction of corneal astigmatism. The IOL selection is based on keratometric measurements of the central cornea. However, mid-peripheral corneal changes may yield suboptimal correction in patients with larger pupils. This study retrospectively analyzed corneal topography data collected using a Scheimpflug device during routine clinical examinations. Of 11,953 patients, 641 met the inclusion criteria. Total corneal astigmatism was compared between five concentric zones (2–6 mm) using vector analysis. The absolute difference between astigmatism at 2 mm and 6 mm was 0.30 D (− 0.36 to 0.64), which decreased to 0.10 D (0 to 0.20) between the 5- and 6-mm zone. With-the-rule astigmatism was the most prevalent (53%), 34% had against-the-rule (ATR), and 13% had oblique. The decrease of the cylinder power with the diameter differed significantly between the three types, with ATR and oblique astigmatism being associated with the steepest change. Patients with high corneal astigmatism tend to demonstrate larger differences between the center and mid-periphery than those with low and moderate astigmatism. In conclusion, we demonstrated that central corneal astigmatism differs from that measured at the mid-periphery and that a larger difference was found in patients with ATR, oblique and high astigmatism.
Complement C3 identified as a unique risk factor for disease severity among young COVID-19 patients in Wuhan, China
Authors: Cheng Weiting , Hornung Roman , Xu Kai , Yang Cai hong , Li Jian
Published: April 2021

Given that a substantial proportion of the subgroup of COVID-19 patients that face a severe disease course are younger than 60 years, it is critical to understand the disease-specific characteristics of young COVID-19 patients. Risk factors for a severe disease course for young COVID-19 patients and possible non-linear influences remain unknown. Data were analyzed from COVID-19 patients with clinical outcome in a single hospital in Wuhan, China, collected retrospectively from Jan 24th to Mar 27th. Clinical, demographic, treatment and laboratory data were collected from patients' medical records. Uni- and multivariable analysis using logistic regression and random forest, with the latter allowing the study of non-linear influences, were performed to investigate the clinical characteristics of a severe disease course. A total of 762 young patients (median age 47 years, interquartile range [IQR] 38–55, range 18–60; 55.9% female) were included, as well as 714 elderly patients as a comparison group. Among the young patients, 362 (47.5%) had a severe/critical disease course and the mean age was statistically significantly higher in the severe subgroup than in the mild subgroup (59.3 vs. 56.0, Student's t-test: p < 0.001). The uni- and multivariable analysis suggested that several covariates such as elevated levels of serum amyloid A (SAA), C-reactive protein (CRP) and lactate dehydrogenase (LDH), and decreased lymphocyte counts influence disease severity independently of age. Elevated levels of complement C3 (odds ratio [OR] 15.6, 95% CI 2.41–122.3; p = 0.039) are particularly associated with the risk of developing severe COVID-19 specifically in young patients, whereas no such influence seems to exist for elderly patients. Additional analysis suggests that the influence of complement C3 in young patients is independent of age, gender, and comorbidities. Variable importance values and partial dependence plots obtained using random forests delivered additional insights, in particular indicating non-linear influences of risk factors on disease severity. This study identified increased levels of complement C3 as a unique risk factor for adverse outcomes specific to young COVID-19 patients.
Design, synthesis and docking studies of novel thiazole derivatives incorporating pyridine moiety and assessment as antimicrobial agents
Authors: Khidre Rizk E. , Radini Ibrahim Ali M.
Published: April 2021

A novel series of substituted 4,6-dimethyl-2-oxo-1-(thiazol-2-ylamino)-1,2-dihydropyridine-3-carbonitrile derivatives 6, 9, 13, 15, and 17 was synthesized in a good to excellent yield from the reaction of 1-(3-cyano-4,6-dimethyl-2-oxopyridin-1(2H)-yl)thiourea with 2-oxo-N'-arylpropanehydrazonoyl chloride, chloroacetone, α-bromoketones, ethyl chloroacetate, and 2,3-dichloroquinoxaline, respectively. The potential DNA gyrase inhibitory activity was examined using in silico molecular docking simulation. The novel thiazoles exhibit dock score values between − 6.4 and − 9.2 kcal/mol and they were screened for their antimicrobial activities. Compound 13a shown good antibacterial activities with MIC ranged from 93.7–46.9 μg/mL, in addition, it shown good antifungal activities with MIC ranged from 7.8 and 5.8 μg/mL.
Future behavior of wind wave extremes due to climate change
Authors: Lobeto Hector , Menendez Melisa , Losada Iñigo J.
Published: April 2021

Extreme waves will undergo changes in the future when exposed to different climate change scenarios. These changes are evaluated through the analysis of significant wave height (Hs) return values and are also compared with annual mean Hs projections. Hourly time series are analyzed through a seven-member ensemble of wave climate simulations and changes are estimated in Hs for return periods from 5 to 100 years by the end of the century under RCP4.5 and RCP8.5 scenarios. Despite the underlying uncertainty that characterizes extremes, we obtain robust changes in extreme Hs over more than approximately 25% of the ocean surface. The results obtained conclude that increases cover wider areas and are larger in magnitude than decreases for higher return periods. The Southern Ocean is the region where the most robust increase in extreme Hs is projected, showing local increases of over 2 m regardless the analyzed return period under RCP8.5 scenario. On the contrary, the tropical north Pacific shows the most robust decrease in extreme Hs, with local decreases of over 1.5 m. Relevant divergences are found in several ocean regions between the projected behavior of mean and extreme wave conditions. For example, an increase in Hs return values and a decrease in annual mean Hs is found in the SE Indian, NW Atlantic and NE Pacific. Therefore, an extrapolation of the expected change in mean wave conditions to extremes in regions presenting such divergences should be adopted with caution, since it may lead to misinterpretation when used for the design of marine structures or in the evaluation of coastal flooding and erosion.
Acoustically induced transparency for synchrotron hard x-ray photons
Authors: Khairulin I. R. , Radeonychev Y. V. , Antonov V. A. , Kocharovskaya Olga
Published: April 2021

The induced transparency of opaque medium for resonant electromagnetic radiation is a powerful tool for manipulating the field-matter interaction. Various techniques to make different physical systems transparent for radiation from microwaves to x-rays were implemented. Most of them are based on the modification of the quantum-optical properties of the medium under the action of an external coherent electromagnetic field. Recently, an observation of acoustically induced transparency (AIT) of the 57Fe absorber for resonant 14.4-keV photons from the radioactive 57Co source was reported. About 150-fold suppression of the resonant absorption of photons due to collective acoustic oscillations of the nuclei was demonstrated. In this paper, we extend the AIT phenomenon to a novel phase-locked regime, when the transmitted photons are synchronized with the absorber vibration. We show that the advantages of synchrotron Mössbauer sources such as the deterministic periodic emission of radiation and controlled spectral-temporal characteristics of the emitted photons along with high-intensity photon flux in a tightly focused beam, make it possible to efficiently implement this regime, paving the way for the development of the acoustically controlled interface between hard x-ray photons and nuclear ensembles.
Characterizing bulk rigidity of rigid red blood cell populations in sickle-cell disease patients
Authors: Gutierrez Mario , Shamoun Mark , Seu Katie Giger , Tanski Tyler , Kalfa Theodosia A. , Eniola-Adefeso Omolola
Published: April 2021

In this work, we utilized a parameterization model of ektacytometry to quantify the bulk rigidity of the rigid red blood cell (RBC) population in sickle cell disease (SCD) patients. Current ektacytometry techniques implement laser diffraction viscometry to estimate the RBC deformability in a whole blood sample. However, the diffraction measurement is an average of all cells present in the measured sample. By coupling an existing parameterization model of ektacytometry to an artificially rigid RBC model, we formulated an innovative system for estimating the average rigidity of the rigid RBC population in SCD blood. We demonstrated that this method could more accurately determine the bulk stiffness of the rigid RBC populations. This information could potentially help develop the ektacytometry technique as a tool for assessing disease severity in SCD patients, offering novel insights into the disease pathology and treatment.
The long noncoding RNA of RMRP is downregulated by PERK, which induces apoptosis in hepatocellular carcinoma cells
Authors: Yukimoto Atsushi , Watanabe Takao , Sunago Kotaro , Nakamura Yoshiko , Tanaka Takaaki , Koizumi Yohei , Yoshida Osamu , Tokumoto Yoshio , Hirooka Masashi , Abe Masanori , Hiasa Yoichi
Published: April 2021

Endoplasmic reticulum (ER) stress plays an important role in hepatocyte degeneration, especially in patients with chronic liver injury. Protein kinase R-like endoplasmic reticulum kinase (PERK) is a key molecule in ER stress. PERK may contribute to apoptotic cell death in HCC, however the details of the mechanism are not clear. In this study, we identified PERK-associated molecules using transcriptome analysis. We modulated PERK expression using a plasmid, tunicamycin and siRNA against PERK, and then confirmed the target gene expression with real-time PCR and Northern blotting. We further analyzed the apoptotic function. Transcriptome analysis revealed that expression of the RNA component of mitochondrial RNA processing endoribonuclease (RMRP), which is a long noncoding RNA, was strongly correlated with the function of PERK. The expression of RMRP was correlated with the expression of PERK in experiments with the siRNA and PERK plasmid in both HCC cell lines and human HCC tissue. Furthermore, RMRP downregulation induced apoptotic cell death. RMRP is downregulated by PERK, which induces apoptosis in HCC. RMRP could be a new therapeutic target to regulate HCC in patients with chronic liver diseases associated with ER stress.
Dyskinesia estimation during activities of daily living using wearable motion sensors and deep recurrent networks
Authors: Hssayeni Murtadha D. , Jimenez-Shahed Joohi , Burack Michelle A. , Ghoraani Behnaz
Published: April 2021

Levodopa-induced dyskinesias are abnormal involuntary movements experienced by the majority of persons with Parkinson’s disease (PwP) at some point over the course of the disease. Choreiform as the most common phenomenology of levodopa-induced dyskinesias can be managed by adjusting the dose/frequency of PD medication(s) based on a PwP’s motor fluctuations over a typical day. We developed a sensor-based assessment system to provide such information. We used movement data collected from the upper and lower extremities of 15 PwPs along with a deep recurrent model to estimate dyskinesia severity as they perform different activities of daily living (ADL). Subjects performed a variety of ADLs during a 4-h period while their dyskinesia severity was rated by the movement disorder experts. The estimated dyskinesia severity scores from our model correlated highly with the expert-rated scores (r= 0.87 (p< 0.001)), which was higher than the performance of linear regression that is commonly used for dyskinesia estimation (r= 0.81 (p< 0.001)). Our model provided consistent performance at different ADLs with minimumr= 0.70 (during walking) to maximumr= 0.84 (drinking) in comparison to linear regression withr= 0.00 (walking) tor= 0.76 (cutting food). These findings suggest that when our model is applied to at-home sensor data, it can provide an accurate picture of changes of dyskinesia severity facilitating effective medication adjustments.
Nanopore long-read RNA-seq and absolute quantification delineate transcription dynamics in early embryo development of an insect pest
Authors: Bayega Anthony , Oikonomopoulos Spyros , Gregoriou Maria-Eleni , Tsoumani Konstantina T. , Giakountis Antonis , Wang Yu Chang , Mathiopoulos Kostas D. , Ragoussis Jiannis
Published: April 2021

The olive fruit fly, Bactrocera oleae, is the most important pest for the olive fruit but lacks adequate transcriptomic characterization that could aid in molecular control approaches. We apply nanopore long-read RNA-seq with internal RNA standards allowing absolute transcript quantification to analyze transcription dynamics during early embryo development for the first time in this organism. Sequencing on the MinION platform generated over 31 million reads. Over 50% of the expressed genes had at least one read covering its entire length validating our full-length approach. We generated a de novo transcriptome assembly and identified 1768 new genes and a total of 79,810 isoforms; a fourfold increase in transcriptome diversity compared to the current NCBI predicted transcriptome. Absolute transcript quantification per embryo allowed an insight into the dramatic re-organization of maternal transcripts. We further identified Zelda as a possible regulator of early zygotic genome activation in B. oleae and provide further insights into the maternal-to-zygotic transition. These data show the utility of long-read RNA in improving characterization of non-model organisms that lack a fully annotated genome, provide potential targets for sterile insect technic approaches, and provide the first insight into the transcriptome landscape of the developing olive fruit fly embryo.
Farm use of calcium hydroxide as an effective barrier against pathogens
Authors: Matsuzaki Shinji , Azuma Kento , Lin Xuguang , Kuragano Masahiro , Uwai Koji , Yamanaka Shinya , Tokuraku Kiyotaka
Published: April 2021

Livestock farming is affected by the occurrence of infectious diseases, but outbreaks can be prevented by proper sanitary control measures. Calcium hydroxide (Ca(OH)2), commonly called slaked lime, powder is traditionally used as a disinfectant to prevent infectious diseases in livestock. Since Ca(OH)2 can inactivate a wide variety of pathogens, has a small environmental impact, does not require a disinfection tank (i.e., can be spread directly on the ground) and is produced inexpensively worldwide, it is used for the prevention of epidemics on farms worldwide. Water is essential for the strong alkalinity that underlies its disinfecting effect, but it is unknown how much water is required under field conditions. In addition, Ca(OH)2 reacts with carbon dioxide in the environment, reducing its pH, but it is unclear how long its degradation takes under actual field use. Thus, we measured the water adsorption ability of Ca(OH)2-based disinfectants and its relation to disinfectant activity, as assessed by colony counts and live/dead staining and observation. We found that 15–20% (w/w) water in Ca(OH)2 was necessary for disinfection to occur in practice. Moreover, we found that the pH of Ca(OH)2 decreased within about two weeks to one month under actual use in practical conditions and lost its ability to disinfect. We further showed that granules prepared from Ca(OH)2 and zeolite maintained high alkalinity more than twice as long as calcium powder. These findings will help to establish a suitable method of applying Ca(OH)2 to protect farms from infectious diseases.
Respiratory adaptation to climate in modern humans and Upper Palaeolithic individuals from Sungir and Mladeč
Authors: Stansfield Ekaterina , Mitteroecker Philipp , Vasilyev Sergey Y. , Vasilyev Sergey , Butaric Lauren N.
Published: April 2021

As our human ancestors migrated into Eurasia, they faced a considerably harsher climate, but the extent to which human cranial morphology has adapted to this climate is still debated. In particular, it remains unclear when such facial adaptations arose in human populations. Here, we explore climate-associated features of face shape in a worldwide modern human sample using 3D geometric morphometrics and a novel application of reduced rank regression. Based on these data, we assess climate adaptations in two crucial Upper Palaeolithic human fossils, Sungir and Mladeč, associated with a boreal-to-temperate climate. We found several aspects of facial shape, especially the relative dimensions of the external nose, internal nose and maxillary sinuses, that are strongly associated with temperature and humidity, even after accounting for autocorrelation due to geographical proximity of populations. For these features, both fossils revealed adaptations to a dry environment, with Sungir being strongly associated with cold temperatures and Mladeč with warm-to-hot temperatures. These results suggest relatively quick adaptative rates of facial morphology in Upper Palaeolithic Europe.
Genome-wide discovery of G-quadruplexes in barley
Authors: Cagirici H. Busra , Budak Hikmet , Sen Taner Z.
Published: April 2021

G-quadruplexes (G4s) are four-stranded nucleic acid structures with closely spaced guanine bases forming square planar G-quartets. Aberrant formation of G4 structures has been associated with genomic instability. However, most plant species are lacking comprehensive studies of G4 motifs. In this study, genome-wide identification of G4 motifs in barley was performed, followed by a comparison of genomic distribution and molecular functions to other monocot species, such as wheat, maize, and rice. Similar to the reports on human and some plants like wheat, G4 motifs peaked around the 5′ untranslated region (5′ UTR), the first coding domain sequence, and the first intron start sites on antisense strands. Our comparative analyses in human, Arabidopsis, maize, rice, and sorghum demonstrated that the peak points could be erroneously merged into a single peak when large window sizes are used. We also showed that the G4 distributions around genic regions are relatively similar in the species studied, except in the case of Arabidopsis. G4 containing genes in monocots showed conserved molecular functions for transcription initiation and hydrolase activity. Additionally, we provided examples of imperfect G4 motifs.
Predicting the crystal structure of $$\hbox {N}_5\hbox {AsF}_6$$ high energy density material using ab initio evolutionary algorithms
Authors: Benchafia El Mostafa , Wang Xianqin , Iqbal Zafar , Abedrabbo Sufian
Published: April 2021

$$\hbox {N}_5\hbox {AsF}_6$$

N
5

AsF
6

is the first successfully synthesized salt that has a polymeric nitrogen moeity ($$\hbox {N}_5^+$$

N
5
+

). Although 12 other $$\hbox {N}_5^+$$

N
5
+

salts followed, with $$\hbox {N}_5\hbox {SbF}_6$$

N
5

SbF
6

and $$\hbox {N}_5\hbox {Sb}_2\hbox {F}_{11}$$

N
5

Sb
2

F
11

being the most stable, the crystal structure of $$\hbox {N}_5\hbox {AsF}_6$$

N
5

AsF
6

remains unknown. Currently, it is impossible to experimentally determine the structures of $$\hbox {N}_5\hbox {AsF}_6$$

N
5

AsF
6

due to its marginal stability and explosive nature. Here, following an ab initio evolutionary prediction and using only the stoichiometry of $$\hbox {N}_5\hbox {AsF}_6$$

N
5

AsF
6

as a starting point, we were able to reveal the crystal structure of this high energy density material (HEDM). The $$\hbox {C}_{2V}$$

C

2
V

symmetry of the $$\hbox {N}_5^+$$

N
5
+

cation, as suggested from earlier investigations, is confirmed to be the symmetry adopted by this polymeric nitrogen within the crystal. This result gave full confidence in the validity of this crystal prediction approach. While stability of the $$\hbox {N}_5^+$$

N
5
+

within the crystal is found to be driven by electronic considerations, the marginal stability of this HEDM is found to be related to a partial softening of its phonon modes.
Vagal control of the heart decreases during increasing imminence of interoceptive threat in patients with panic disorder and agoraphobia
Authors: Richter Jan , Pietzner Anne , Koenig Julian , Thayer Julian F. , Pané-Farré Christiane A. , Gerlach Alexander L. , Gloster Andrew T. , Wittchen Hans-Ulrich , Lang Thomas , Alpers Georg W. , Helbig-Lang Sylvia , Deckert Jürgen , Fydrich Thomas , Fehm Lydia , Ströhle Andreas , Kircher Tilo , Arolt Volker , Hamm Alfons O.
Published: April 2021

Theoretically, panic disorder and agoraphobia pathology can be conceptualized as a cascade of dynamically changing defensive responses to threat cues from inside the body. Guided by this trans-diagnostic model we tested the interaction between defensive activation and vagal control as a marker of prefrontal inhibition of subcortical defensive activation. We investigated ultra-short-term changes of vagally controlled high frequency heart rate variability (HRV) during a standardized threat challenge (entrapment) in n = 232 patients with panic disorder and agoraphobia, and its interaction with various indices of defensive activation. We found a strong inverse relationship between HRV and heart rate during threat, which was stronger at the beginning of exposure. Patients with a strong increase in heart rate showed a deactivation of prefrontal vagal control while patients showing less heart rate acceleration showed an increase in vagal control. Moreover, vagal control collapsed in case of imminent threat, i.e., when body symptoms increase and seem to get out of control. In these cases of defensive action patients either fled from the situation or experienced a panic attack. Active avoidance, panic attacks, and increased sympathetic arousal are associated with an inability to maintain vagal control over the heart suggesting that teaching such regulation strategies during exposure treatment might be helpful to keep prefrontal control, particularly during the transition zone from post-encounter to circa strike defense.

Trial Registration Number: ISRCTN80046034.
CD25890, a conserved protein that modulates sporulation initiation in Clostridioides difficile
Authors: Martins Diogo , DiCandia Michael A. , Mendes Aristides L. , Wetzel Daniela , McBride Shonna M. , Henriques Adriano O. , Serrano Mónica
Published: April 2021

Bacteria that reside in the gastrointestinal tract of healthy humans are essential for our health, sustenance and well-being. About 50–60% of those bacteria have the ability to produce resilient spores that are important for the life cycle in the gut and for host-to-host transmission. A genomic signature for sporulation in the human intestine was recently described, which spans both commensals and pathogens such as Clostridioides difficile and contains several genes of unknown function. We report on the characterization of a signature gene, CD25890, which, as we show is involved in the control of sporulation initiation in C. difficile under certain nutritional conditions. Spo0A is the main regulatory protein controlling entry into sporulation and we show that an in-frame deletion of CD25890 results in increased expression of spo0A per cell and increased sporulation. The effect of CD25890 on spo0A is likely indirect and mediated through repression of the sinRR´ operon. Deletion of the CD25890 gene, however, does not alter the expression of the genes coding for the cytotoxins or the genes involved in biofilm formation. Our results suggest that CD25890 acts to modulate sporulation in response to the nutrients present in the environment.
High-pulse-energy multiphoton imaging of neurons and oligodendrocytes in deep murine brain with a fiber laser
Authors: Redlich Michael J. , Prall Brad , Canto-Said Edesly , Busarov Yevgeniy , Shirinyan-Tuka Lilit , Meah Arafat , Lim Hyungsik
Published: April 2021

Here we demonstrate high-pulse-energy multiphoton microscopy (MPM) for intravital imaging of neurons and oligodendrocytes in the murine brain. Pulses with an order of magnitude higher energy (~ 10 nJ) were employed from a ytterbium doped fiber laser source at a 1-MHz repetition rate, as compared to the standard 80-MHz Ti:Sapphire laser. Intravital imaging was performed on mice expressing common fluorescent proteins, including green (GFP) and yellow fluorescent proteins (YFP), and TagRFPt. One fifth of the average power could be used for superior depths of MPM imaging, as compared to the Ti:Sapphire laser: A depth of ~ 860 µm was obtained by imaging the Thy1-YFP brain in vivo with 6.5 mW, and cortical myelin as deep as 400 µm ex vivo by intrinsic third-harmonic generation using 50 mW. The substantially higher pulse energy enables novel regimes of photophysics to be exploited for microscopic imaging. The limitation from higher order phototoxicity is also discussed.