bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid, adaptable and sensitive Cas13-based COVID-19 diagnostics using ADESSO
Authors: Casati Beatrice , Verdi Joseph Peter , Hempelmann Alexander , Kittel Maximilian , Klaebisch Andrea Gutierrez , Meister Bianca , Welker Sybille , Asthana Sonal , Di Giorgio Salvatore , Boskovic Pavle , Man Ka Hou , Schopp Meike , Ginno Paul Adrian , Radlwimmer Bernhard , Stebbins Charles Erec , Miethke Thomas , Papavasiliou Fotini Nina , Pecori Riccardo 
Published: June 2022

AbstractDuring the ongoing COVID-19 pandemic, PCR testing and antigen tests have proven critical for helping to stem the spread of its causative agent, SARS-CoV-2. However, these methods suffer from either general applicability and/or sensitivity. Moreover, the emergence of variant strains creates the need for flexibility to correctly and efficiently diagnose the presence of substrains. To address these needs we developed the diagnostic test ADESSO (Accurate Detection of Evolving SARS-CoV-2 through SHERLOCK (Specific High Sensitivity Enzymatic Reporter UnLOCKing) Optimization) which employs Cas13 to diagnose patients in 1 h without sophisticated equipment. Using an extensive panel of clinical samples, we demonstrate that ADESSO correctly identifies infected individuals at a sensitivity and specificity comparable to RT-qPCR on extracted RNA and higher than antigen tests for unextracted samples. Altogether, ADESSO is a fast, sensitive and cheap method that can be applied in a point of care setting to diagnose COVID-19 and can be quickly adjusted to detect new variants.
Leukocyte cell-derived chemotaxin 2 is an antiviral regulator acting through the proto-oncogene MET
Authors: Shirasaki Takayoshi , Yamagoe Satoshi , Shimakami Tetsuro , Murai Kazuhisa , Imamura Ryu , Ishii Kiyo-Aki , Takayama Hiroaki , Matsumoto Yukako , Tajima-Shirasaki Natsumi , Nagata Naoto , Shimizu Ryogo , Yamanaka Souma , Abe Atsushi , Omura Hitoshi , Kawaguchi Kazunori , Okada Hikari , Yamashita Taro , Yoshikawa Tomoki , Takimoto Kazuhiro , Taharaguchi Motoko , Takatsuka Shogo , Miyazaki Yoshitsugu , Tamai Toshikatsu , Tanabe Yamato , Kurachi Makoto , Yamamoto Yasuhiko , Kaneko Shuichi , Matsumoto Kunio , Takamura Toshinari , Honda Masao 
Published: June 2022

AbstractRetinoic acid-inducible gene (RIG)-I is an essential innate immune sensor that recognises pathogen RNAs and induces interferon (IFN) production. However, little is known about how host proteins regulate RIG-I activation. Here, we show that leukocyte cell-derived chemotaxin 2 (LECT2), a hepatokine and ligand of the MET receptor tyrosine kinase is an antiviral regulator that promotes the RIG-I-mediated innate immune response. Upon binding to MET, LECT2 induces the recruitment of the phosphatase PTP4A1 to MET and facilitates the dissociation and dephosphorylation of phosphorylated SHP2 from MET, thereby protecting RIG-I from SHP2/c-Cbl-mediated degradation. In vivo, LECT2 overexpression enhances RIG-I-dependent IFN production and inhibits lymphocytic choriomeningitis virus (LCMV) replication in the liver, whereas these changes are reversed in LECT2 knockout mice. Forced suppression of MET abolishes IFN production and antiviral activity in vitro and in vivo. Interestingly, hepatocyte growth factor (HGF), an original MET ligand, inhibits LECT2-mediated anti-viral signalling; conversely, LECT2-MET signalling competes with HGF-MET signalling. Our findings reveal previously unrecognized crosstalk between MET-mediated proliferation and innate immunity and suggest that targeting LECT2 may have therapeutic value in infectious diseases and cancer.
Integration of multiple electronic components on a microfibre towards an emerging electronic textile platform
Authors: Hwang Sunbin , Kang Minji , Lee Aram , Bae Sukang , Lee Seoung-Ki , Lee Sang Hyun , Lee Takhee , Wang Gunuk , Kim Tae-Wook 
Published: June 2022

AbstractElectronic fibres have been considered one of the desired device platforms due to their dimensional compatibility with fabrics by weaving with yarns. However, a precise connecting process between each electronic fibre is essential to configure the desired electronic circuits or systems. Here, we present an integrated electronic fibre platform by fabricating electronic devices onto a one-dimensional microfibre substrate. Electronic components such as transistors, inverters, ring oscillators, and thermocouples are integrated together onto the outer surface of a fibre substrate with precise semiconductor and electrode patterns. Our results show that electronic components can be integrated on a single fibre with reliable operation. We evaluate the electronic properties of the chip on the fibre as a multifunctional electronic textile platform by testing their switching and data processing, as well as sensing or transducing units for detecting optical/thermal signals. The demonstration of the electronic fibre suggests significant proof of concepts for the realization of high performance with wearable electronic textile systems.
Ligand recognition and biased agonism of the D1 dopamine receptor
Authors: Teng Xiao , Chen Sijia , Nie Yingying , Xiao Peng , Yu Xiao , Shao Zhenhua , Zheng Sanduo 
Published: June 2022

AbstractDopamine receptors are widely distributed in the central nervous system and are important therapeutic targets for treatment of various psychiatric and neurological diseases. Here, we report three cryo-electron microscopy structures of the D1 dopamine receptor (D1R)-Gs complex bound to two agonists, fenoldopam and tavapadon, and a positive allosteric modulator LY3154207. The structure reveals unusual binding of two fenoldopam molecules, one to the orthosteric binding pocket (OBP) and the other to the extended binding pocket (EBP). In contrast, one elongated tavapadon molecule binds to D1R, extending from OBP to EBP. Moreover, LY3154207 stabilizes the second intracellular loop of D1R in an alpha helical conformation to efficiently engage the G protein. Through a combination of biochemical, biophysical and cellular assays, we further show that the broad conformation stabilized by two fenoldopam molecules and interaction between TM5 and the agonist are important for biased signaling of D1R.
Deep learning enables reference-free isotropic super-resolution for volumetric fluorescence microscopy
Authors: Park Hyoungjun , Na Myeongsu , Kim Bumju , Park Soohyun , Kim Ki Hean , Chang Sunghoe , Ye Jong Chul 
Published: June 2022

AbstractVolumetric imaging by fluorescence microscopy is often limited by anisotropic spatial resolution, in which the axial resolution is inferior to the lateral resolution. To address this problem, we present a deep-learning-enabled unsupervised super-resolution technique that enhances anisotropic images in volumetric fluorescence microscopy. In contrast to the existing deep learning approaches that require matched high-resolution target images, our method greatly reduces the effort to be put into practice as the training of a network requires only a single 3D image stack, without a priori knowledge of the image formation process, registration of training data, or separate acquisition of target data. This is achieved based on the optimal transport-driven cycle-consistent generative adversarial network that learns from an unpaired matching between high-resolution 2D images in the lateral image plane and low-resolution 2D images in other planes. Using fluorescence confocal microscopy and light-sheet microscopy, we demonstrate that the trained network not only enhances axial resolution but also restores suppressed visual details between the imaging planes and removes imaging artifacts.
Allelic expression imbalance of PIK3CA mutations is frequent in breast cancer and prognostically significant
Authors: Correia Lizelle , Magno Ramiro , Xavier Joana M. , de Almeida Bernardo P. , Duarte Isabel , Esteves Filipa , Ghezzo Marinella , Eldridge Matthew , Sun Chong , Bosma Astrid , Mittempergher Lorenza , Marreiros Ana , Bernards Rene , Caldas Carlos , Chin Suet-Feung , Maia Ana-Teresa 
Published: June 2022

AbstractPIK3CA mutations are the most common in breast cancer, particularly in the estrogen receptor-positive cohort, but the benefit of PI3K inhibitors has had limited success compared with approaches targeting other less common mutations. We found a frequent allelic expression imbalance between the missense mutant and wild-type PIK3CA alleles in breast tumors from the METABRIC (70.2%) and the TCGA (60.1%) projects. When considering the mechanisms controlling allelic expression, 27.7% and 11.8% of tumors showed imbalance due to regulatory variants in cis, in the two studies respectively. Furthermore, preferential expression of the mutant allele due to cis-regulatory variation is associated with poor prognosis in the METABRIC tumors (P = 0.031). Interestingly, ER−, PR−, and HER2+ tumors showed significant preferential expression of the mutated allele in both datasets. Our work provides compelling evidence to support the clinical utility of PIK3CA allelic expression in breast cancer in identifying patients of poorer prognosis, and those with low expression of the mutated allele, who will unlikely benefit from PI3K inhibitors. Furthermore, our work proposes a model of differential regulation of a critical cancer-promoting gene in breast cancer.
Anisotropic Dzyaloshinskii-Moriya interaction protected by D2d crystal symmetry in two-dimensional ternary compounds
Authors: Ga Yonglong , Cui Qirui , Zhu Yingmei , Yu Dongxing , Wang Liming , Liang Jinghua , Yang Hongxin 
Published: June 2022

AbstractMagnetic skyrmions, topologically protected chiral spin swirling quasiparticles, have attracted great attention in fundamental physics and applications. Recently, the discovery of two-dimensional (2D) van der Waals (vdW) magnets have aroused great interest due to their appealing physical properties. Moreover, both experimental and theoretical works have revealed that isotropic Dzyaloshinskii–Moriya interaction (DMI) can be achieved in 2D magnets or ferromagnet-based heterostructures. However, 2D magnets with anisotropic DMI haven’t been reported yet. Here, via using first-principles calculations, we unveil that anisotropic DMI protected by D2d crystal symmetry can exist in 2D ternary compounds MCuX2 (M: 3d transition metal (TM), X: group VIA). Interestingly, by using micromagnetic simulations, we demonstrate that ferromagnetic (FM) antiskyrmions, FM bimerons, antiferromagnetic (AFM) antiskyrmions, and AFM bimerons can be realized in the MCuX2 family. Our discovery opens up an avenue to creating antiskyrmions and bimerons with anisotropic DMI protected by D2d crystal symmetry in 2D magnets.
Enhancing the precision limits of interferometric satellite geodesy missions
Authors: Conlon Lorcán O. , Michel Thibault , Guccione Giovanni , McKenzie Kirk , Assad Syed M. , Lam Ping Koy 
Published: June 2022

AbstractSatellite geodesy uses the measurement of the motion of one or more satellites to infer precise information about the Earth’s gravitational field. In this work, we consider the achievable precision limits on such measurements by examining approximate models for the three main noise sources in the measurement process of the current Gravitational Recovery and Climate Experiment (GRACE) Follow-On mission: laser phase noise, accelerometer noise and quantum noise. We show that, through time-delay interferometry, it is possible to remove the laser phase noise from the measurement, allowing for almost three orders of magnitude improvement in the signal-to-noise ratio. Several differential mass satellite formations are presented which can further enhance the signal-to-noise ratio through the removal of accelerometer noise. Finally, techniques from quantum optics have been studied, and found to have great promise for reducing quantum noise in other alternative mission configurations. We model the spectral noise performance using an intuitive 1D model and verify that our proposals have the potential to greatly enhance the performance of near-future satellite geodesy missions.
Solar flare accelerates nearly all electrons in a large coronal volume
Authors: Fleishman Gregory D. , Nita Gelu M. , Chen Bin , Yu Sijie , Gary Dale E. 
Published: June 2022

AbstractSolar flares, driven by prompt release of free magnetic energy in the solar corona1,2, are known to accelerate a substantial portion (ten per cent or more)3,4 of available electrons to high energies. Hard X-rays, produced by high-energy electrons accelerated in the flare5, require a high ambient density for their detection. This restricts the observed volume to denser regions that do not necessarily sample the entire volume of accelerated electrons6. Here we report evolving spatially resolved distributions of thermal and non-thermal electrons in a solar flare derived from microwave observations that show the true extent of the acceleration region. These distributions show a volume filled with only (or almost only) non-thermal electrons while being depleted of the thermal plasma, implying that all electrons have experienced a prominent acceleration there. This volume is isolated from a surrounding, more typical flare plasma of mainly thermal particles with a smaller proportion of non-thermal electrons. This highly efficient acceleration happens in the same volume in which the free magnetic energy is being released2.
Mechanism of mitoribosomal small subunit biogenesis and preinitiation
Authors: Itoh Yuzuru , Khawaja Anas , Laptev Ivan , Cipullo Miriam , Atanassov Ilian , Sergiev Petr , Rorbach Joanna , Amunts Alexey 
Published: June 2022

AbstractMitoribosomes are essential for the synthesis and maintenance of bioenergetic proteins. Here we use cryo-electron microscopy to determine a series of the small mitoribosomal subunit (SSU) intermediates in complex with auxiliary factors, revealing a sequential assembly mechanism. The methyltransferase TFB1M binds to partially unfolded rRNA h45 that is promoted by RBFA, while the mRNA channel is blocked. This enables binding of METTL15 that promotes further rRNA maturation and a large conformational change of RBFA. The new conformation allows initiation factor mtIF3 to already occupy the subunit interface during the assembly. Finally, the mitochondria-specific ribosomal protein mS37 (ref. 1) outcompetes RBFA to complete the assembly with the SSU–mS37–mtIF3 complex2 that proceeds towards mtIF2 binding and translation initiation. Our results explain how the action of step-specific factors modulate the dynamic assembly of the SSU, and adaptation of a unique protein, mS37, links the assembly to initiation to establish the catalytic human mitoribosome.
PeSTK db a comprehensive data repository of Probiotic Serine Threonine kinases
Authors: Lokesh Dhanashree , PSN Suresh , Kammara Rajagopal 
Published: June 2022

AbstractThe signal transduction pathway of prokaryotes involves a peptidoglycan synthesis cluster (PG) to sense external stimuli. One of the major components of the PG synthesis cluster is protein kinases (pknA - G). The sequence data of probiotic eSTKs (Eukaryotic like Serine, Threonine kinases) are obscure, scarce and essentially required to understand the role of probiotic microbes in combating infectious diseases. The most essential need to understand and develop certain therapeutic drugs against pathogens is the eSTK sequence data. Hence, we developed a comprehensive user-friendly data repository of probiotic eSTK’s (PeSTK), which holds 830 STK sequences. Therefore, the data resource of PeSTK developed is unique, an open-access very summative containing various probiotic eSTK’s in a single locality. The sequence datasets of the eSTK developed with easy-to-operate browsing as well as searching. Therefore, eSTK data resources should be useful for sequence-based studies and drug development. The sequence datasets are available at Figshare Digital Object Identifier/DOI of the sequences is https://doi.org/10.6084/m9.figshare.146606.
Assessment of pavement deflection under vehicle loads using a 3D-DIC system in the field
Authors: Núñez-Temes Carlos , Bastos Guillermo , Arza-García Marcos , Castro Alberte , Lorenzana Fernández Jose Antonio , Ortiz-Sanz Juan , Portela María , Gil-Docampo Mariluz , Prego Francisco Javier 
Published: June 2022

AbstractThis study aims to introduce the use of 3D-digital image correlation (DIC) to the in situ testing of pavements and to support the development of techniques for a rapid evaluation of the conservation status of existing roads. Little research was found on this topic. The passage of a car wheel on an asphalt pavement was adopted as a case study. The DIC measurements were compared to those gathered by contact sensors. From a qualitative point of view, the DIC measurements captured the realistic shape of a deflection basin. From a quantitative point of view, the deflection values provided by the DIC system had a mean error of 0.015 mm and a standard deviation of 0.011 mm. At the moment of highest load, these errors had a mean value and standard deviation of − 0.016 mm and 0.021 mm, respectively. Thus, to improve the accuracy of the system, we propose modifying the camera support, speckle pattern, and control of natural light.
Substrate-dependent modulation of the leukotriene A4 hydrolase aminopeptidase activity and effect in a murine model of acute lung inflammation
Authors: Lee Kyung Hyeon , Ali Nadia Fazal , Lee Soo Hyeon , Zhang Zhimin , Burdick Marie , Beaulac Zachary J. , Petruncio Greg , Li Linxia , Xiang Jiangdong , Chung Ezra M. , Foreman Kenneth W. , Noble Schroeder M. , Shim Yun M. , Paige Mikell 
Published: June 2022

AbstractThe aminopeptidase activity (AP) of the leukotriene A4 hydrolase (LTA4H) enzyme has emerged as a therapeutic target to modulate host immunity. Initial reports focused on the benefits of augmenting the LTA4H AP activity and clearing its putative pro-inflammatory substrate Pro-Gly-Pro (PGP). However, recent reports have introduced substantial complexity disconnecting the LTA4H modulator 4-methoxydiphenylmethane (4MDM) from PGP as follows: (1) 4MDM inhibits PGP hydrolysis and subsequently inhibition of LTA4H AP activity, and (2) 4MDM activates the same enzyme target in the presence of alternative substrates. Differential modulation of LTA4H by 4MDM was probed in a murine model of acute lung inflammation, which showed that 4MDM modulates the host neutrophilic response independent of clearing PGP. X-ray crystallography showed that 4MDM and PGP bind at the zinc binding pocket and no allosteric binding was observed. We then determined that 4MDM modulation is not dependent on the allosteric binding of the ligand, but on the N-terminal side chain of the peptide. In conclusion, our study revealed that a peptidase therapeutic target can interact with its substrate and ligand in complex biochemical mechanisms. This raises an important consideration when ligands are designed to explain some of the unpredictable outcomes observed in therapeutic discovery targeting LTA4H.
A waste-to-wealth initiative exploiting the potential of Anabaena variabilis for designing an integrated biorefinery
Authors: Deb Dipanwita , Mallick Nirupama , Bhadoria P. B. S. 
Published: June 2022

AbstractThe current research work was an innovative approach providing dual advantages of waste bioremediation and an effective biorefinery. The study attempted to exploit wastewater like aqua discharge and solid wastes like poultry litter/cow dung for cyanobacterial cultivation. Aqua discharge appended with 7.5 g L−1 poultry litter turned out as the best combination generating 46% higher carbohydrate yield than BG-11 control. A. variabilis cultivation in this waste-utilized medium also revealed its excellent bioremediation ability. While 100% removal was observed for nitrite, nitrate, and orthophosphate, a respective 74% and 81% reduction was noted for ammonium and total organic carbon. Chemical and biological oxygen demands were also reduced by 90%. This work was also novel in developing a sequential design for the production of bioethanol and co-products like exopolysaccharides, sodium copper chlorophyllin, C-phycocyanin, and poly-β-hydroxybutyrate from the same cyanobacterial biomass. The developed biorefinery implementing the waste-utilized medium was one of its kind, enabling biomass valorization of 61%. Therefore, the present study would provide a leading-edge for tackling the high production costs that limit the practical viability of biorefinery projects. The recyclability of the bioremediated wastewater would not only curtail freshwater usage, the waste disposal concerns would also be mitigated to a great extent.
Reading speed in school-age children with intermittent exotropia
Authors: Fang Cheng , Wu Yidong , peng Tingting , Wang Chunxiao , Lou Jiangtao , Xu Meiping , Bao Jinhua , Chen Chonglin , Yu Xinping 
Published: June 2022

AbstractReading speed in intermittent exotropia (IXT) children has been minimally examined. This study assessed reading speed in school-age children with IXT and determined clinical characteristics of IXT that impacted their reading ability. We compared the reading speed of 63 school-age (10–14 years) children with IXT to 44 age-matched normal counterparts. In addition, the correlation between reading speed and clinical characteristics of IXT were evaluated. The reading speed in children with IXT was 231 ± 51 CPM, while reading speed in normal counterparts was 257 ± 33 CPM. Age, gender were found to be factors associated with reading speed in children with IXT. After adjusting for the age and gender, we found a significant correlation between the LogTNO and reading speed in IXT group based on a generalized linear model (p = 0.014). These data show that reading speed was slower in school-age children with IXT assessed with the International Reading Speed Texts. When age and gender were adjusted, poor stereo function at near was found to be related with a slower reading speed.
Association of human milk oligosaccharides and nutritional status of young infants among Bangladeshi mother–infant dyads
Authors: Nuzhat Sharika , Palit Parag , Mahfuz Mustafa , Islam Md. Ridwan , Hasan S. M. Tafsir , Islam M. Munirul , Sarker Shafiqul. A. , Kyle David J. , Flannery Robin L. , Vinjamuri Anita , Lebrilla Carlito B. , Ahmed Tahmeed 
Published: June 2022

AbstractHuman milk oligosaccharides (HMOs) support the development of a healthy gut microbiome and the growth of infants. We aimed to determine the association of different HMOs with severe acute malnutrition (SAM) among Bangladeshi young infants. This study was nested within a single-blind, randomized, pilot clinical trial (NCT0366657). A total of 45 breastmilk samples from mothers of < 6 months old infants who had SAM (n = 26) or were non-malnourished (n = 19) and were analyzed for constituent HMOs. Of the infants with SAM, 14 (53.85%) had secretor mothers, and 11 (57.89%) of the non-malnourished infants had secretor mothers. A one-unit increase in the relative abundance of sialylated HMOs was associated with higher odds of SAM in age and sex adjusted model (aOR = 2.00, 90% CI 1.30, 3.06), in age, sex, and secretor status adjusted model (aOR = 1.96, 90% CI 1.29, 2.98), and also in age and sex adjusted model among non-secretor mothers (aOR = 2.86, 90% CI 1.07, 7.62). In adjusted models, there was no evidence of a statistically significant association between SAM and fucosylated or undecorated HMOs. Our study demonstrates that a higher relative abundance of sialylated HMOs in mothers’ breastmilk may have a negative impact on young infants’ nutritional status.