bluuebunny/crossref_metadata_2025 huggingface dataset:
Blastocyst complementation using Prdm14-deficient rats enables efficient germline transmission and generation of functional mouse spermatids in rats
Authors: Kobayashi Toshihiro , Goto Teppei , Oikawa Mami , Sanbo Makoto , Yoshida Fumika , Terada Reiko , Niizeki Naoko , Kajitani Naoyo , Kazuki Kanako , Kazuki Yasuhiro , Hochi Shinichi , Nakauchi Hiromitsu , Surani M. Azim , Hirabayashi Masumi
Published: February 2021

Murine animal models from genetically modified pluripotent stem cells (PSCs) are essential for functional genomics and biomedical research, which require germline transmission for the establishment of colonies. However, the quality of PSCs, and donor-host cell competition in chimeras often present strong barriers for germline transmission. Here, we report efficient germline transmission of recalcitrant PSCs via blastocyst complementation, a method to compensate for missing tissues or organs in genetically modified animals via blastocyst injection of PSCs. We show that blastocysts from germline-deficient Prdm14 knockout rats provide a niche for the development of gametes originating entirely from the donor PSCs without any detriment to somatic development. We demonstrate the potential of this approach by creating PSC-derived Pax2/Pax8 double mutant anephric rats, and rescuing germline transmission of a PSC carrying a mouse artificial chromosome. Furthermore, we generate mouse PSC-derived functional spermatids in rats, which provides a proof-of-principle for the generation of xenogenic gametes in vivo. We believe this approach will become a useful system for generating PSC-derived germ cells in the future.
Electromechanically reconfigurable optical nano-kirigami
Authors: Chen Shanshan , Liu Zhiguang , Du Huifeng , Tang Chengchun , Ji Chang-Yin , Quan Baogang , Pan Ruhao , Yang Lechen , Li Xinhao , Gu Changzhi , Zhang Xiangdong , Yao Yugui , Li Junjie , Fang Nicholas X. , Li Jiafang
Published: February 2021

Kirigami, with facile and automated fashion of three-dimensional (3D) transformations, offers an unconventional approach for realizing cutting-edge optical nano-electromechanical systems. Here, we demonstrate an on-chip and electromechanically reconfigurable nano-kirigami with optical functionalities. The nano-electromechanical system is built on an Au/SiO2/Si substrate and operated via attractive electrostatic forces between the top gold nanostructure and bottom silicon substrate. Large-range nano-kirigami like 3D deformations are clearly observed and reversibly engineered, with scalable pitch size down to 0.975 μm. Broadband nonresonant and narrowband resonant optical reconfigurations are achieved at visible and near-infrared wavelengths, respectively, with a high modulation contrast up to 494%. On-chip modulation of optical helicity is further demonstrated in submicron nano-kirigami at near-infrared wavelengths. Such small-size and high-contrast reconfigurable optical nano-kirigami provides advanced methodologies and platforms for versatile on-chip manipulation of light at nanoscale.
Structure-guided insights into heterocyclic ring-cleavage catalysis of the non-heme Fe (II) dioxygenase NicX
Authors: Liu Gongquan , Zhao Yi-Lei , He Fangyuan , Zhang Peng , Ouyang Xingyu , Tang Hongzhi , Xu Ping
Published: February 2021

Biodegradation of aromatic and heterocyclic compounds requires an oxidative ring cleavage enzymatic step. Extensive biochemical research has yielded mechanistic insights about catabolism of aromatic substrates; yet much less is known about the reaction mechanisms underlying the cleavage of heterocyclic compounds such as pyridine-ring-containing ones like 2,5-hydroxy-pyridine (DHP). 2,5-Dihydroxypyridine dioxygenase (NicX) from Pseudomonas putida KT2440 uses a mononuclear nonheme Fe(II) to catalyze the oxidative pyridine ring cleavage reaction by transforming DHP into N-formylmaleamic acid (NFM). Herein, we report a crystal structure for the resting form of NicX, as well as a complex structure wherein DHP and NFM are trapped in different subunits. The resting state structure displays an octahedral coordination for Fe(II) with two histidine residues (His265 and His318), a serine residue (Ser302), a carboxylate ligand (Asp320), and two water molecules. DHP does not bind as a ligand to Fe(II), yet its interactions with Leu104 and His105 function to guide and stabilize the substrate to the appropriate position to initiate the reaction. Additionally, combined structural and computational analyses lend support to an apical dioxygen catalytic mechanism. Our study thus deepens understanding of non-heme Fe(II) dioxygenases.
Ultra-bright Raman dots for multiplexed optical imaging
Authors: Zhao Zhilun , Chen Chen , Wei Shixuan , Xiong Hanqing , Hu Fanghao , Miao Yupeng , Jin Tianwei , Min Wei
Published: February 2021

Imaging the spatial distribution of biomolecules is at the core of modern biology. The development of fluorescence techniques has enabled researchers to investigate subcellular structures with nanometer precision. However, multiplexed imaging, i.e. observing complex biological networks and interactions, is mainly limited by the fundamental ‘spectral crowding’ of fluorescent materials. Raman spectroscopy-based methods, on the other hand, have a much greater spectral resolution, but often lack the required sensitivity for practical imaging of biomarkers. Addressing the pressing need for new Raman probes, herein we present a series of Raman-active  nanoparticles (Rdots) that exhibit the combined advantages of ultra-brightness and compact sizes (~20 nm). When coupled with the emerging stimulated Raman scattering (SRS) microscopy, these Rdots are brighter than previously reported Raman-active organic probes by two to three orders of magnitude. We further obtain evidence supporting for SRS imaging of Rdots at single particle level. The compact size and ultra-brightness of Rdots allows immunostaining of specific protein targets (including cytoskeleton and low-abundant surface proteins) in mammalian cells and tissue slices with high imaging contrast. These Rdots thus offer a promising tool for a large range of studies on complex biological networks.
Ultrarobust, tough and highly stretchable self-healing materials based on cartilage-inspired noncovalent assembly nanostructure
Authors: Wang Yuyan , Huang Xin , Zhang Xinxing
Published: February 2021

Self-healing materials integrated with excellent mechanical strength and simultaneously high healing efficiency would be of great use in many fields, however their fabrication has been proven extremely challenging. Here, inspired by biological cartilage, we present an ultrarobust self-healing material by incorporating high density noncovalent bonds at the interfaces between the dentritic tannic acid-modified tungsten disulfide nanosheets and polyurethane matrix to collectively produce a strong interfacial interaction. The resultant nanocomposite material with interwoven network shows excellent tensile strength (52.3 MPa), high toughness (282.7 MJ m‒3, which is 1.6 times higher than spider silk and 9.4 times higher than metallic aluminum), high stretchability (1020.8%) and excellent healing efficiency (80–100%), which overturns the previous understanding of traditional noncovalent bonding self-healing materials where high mechanical robustness and healing ability are mutually exclusive. Moreover, the interfacical supramolecular crosslinking structure enables the functional-healing ability of the resultant flexible smart actuation devices. This work opens an avenue toward the development of ultrarobust self-healing materials for various flexible functional devices.
Comprehensive analysis of single cell ATAC-seq data with SnapATAC
Authors: Fang Rongxin , Preissl Sebastian , Li Yang , Hou Xiaomeng , Lucero Jacinta , Wang Xinxin , Motamedi Amir , Shiau Andrew K. , Zhou Xinzhu , Xie Fangming , Mukamel Eran A. , Zhang Kai , Zhang Yanxiao , Behrens M. Margarita , Ecker Joseph R. , Ren Bing
Published: February 2021

Identification of the cis-regulatory elements controlling cell-type specific gene expression patterns is essential for understanding the origin of cellular diversity. Conventional assays to map regulatory elements via open chromatin analysis of primary tissues is hindered by sample heterogeneity. Single cell analysis of accessible chromatin (scATAC-seq) can overcome this limitation. However, the high-level noise of each single cell profile and the large volume of data pose unique computational challenges. Here, we introduce SnapATAC, a software package for analyzing scATAC-seq datasets. SnapATAC dissects cellular heterogeneity in an unbiased manner and map the trajectories of cellular states. Using the Nyström method, SnapATAC can process data from up to a million cells. Furthermore, SnapATAC incorporates existing tools into a comprehensive package for analyzing single cell ATAC-seq dataset. As demonstration of its utility, SnapATAC is applied to 55,592 single-nucleus ATAC-seq profiles from the mouse secondary motor cortex. The analysis reveals ~370,000 candidate regulatory elements in 31 distinct cell populations in this brain region and inferred candidate cell-type specific transcriptional regulators.
Evaporation-driven transport-control of small molecules along nanoslits
Authors: Seo Sangjin , Ha Dogyeong , Kim Taesung
Published: February 2021

Understanding and controlling the transport mechanisms of small molecules at the micro/nanoscales is vital because they provide a working principle for a variety of practical micro/nanofluidic applications. However, most precedent mechanisms still have remaining obstacles such as complicated fabrication processes, limitations of materials, and undesired damage on samples. Herein, we present the evaporation-driven transport-control of small molecules in gas-permeable and low-aspect ratio nanoslits, wherein both the diffusive and advective mass transports of solutes are affected by solvent evaporation through the nanoslit walls. The effect of the evaporation flux on the mass transport of small molecules in various nanoslit-integrated micro/nanofluidic devices is characterized, and dynamic transport along the nanoslit is investigated by conducting numerical simulations using the advection-diffusion equation. We further demonstrate that evaporation-driven, nanoslit-based transport-control can be easily applied to a micro/nanofluidic channel network in an independent and addressable array, offering a unique working principle for micro/nanofluidic applications and components such as molecule-valves, -concentrators, -pumps, and -filters.
Ecology-guided prediction of cross-feeding interactions in the human gut microbiome
Authors: Goyal Akshit , Wang Tong , Dubinkina Veronika , Maslov Sergei
Published: February 2021

Understanding a complex microbial ecosystem such as the human gut microbiome requires information about both microbial species and the metabolites they produce and secrete. These metabolites are exchanged via a large network of cross-feeding interactions, and are crucial for predicting the functional state of the microbiome. However, till date, we only have information for a part of this network, limited by experimental throughput. Here, we propose an ecology-based computational method, GutCP, using which we predict hundreds of new experimentally untested cross-feeding interactions in the human gut microbiome. GutCP utilizes a mechanistic model of the gut microbiome with the explicit exchange of metabolites and their effects on the growth of microbial species. To build GutCP, we combine metagenomic and metabolomic measurements from the gut microbiome with optimization techniques from machine learning. Close to 65% of the cross-feeding interactions predicted by GutCP are supported by evidence from genome annotations, which we provide for experimental testing. Our method has the potential to greatly improve existing models of the human gut microbiome, as well as our ability to predict the metabolic profile of the gut.
A molecular quantitative trait locus map for osteoarthritis
Authors: Steinberg Julia , Southam Lorraine , Roumeliotis Theodoros I. , Clark Matthew J. , Jayasuriya Raveen L. , Swift Diane , Shah Karan M. , Butterfield Natalie C. , Brooks Roger A. , McCaskie Andrew W. , Bassett J. H. Duncan , Williams Graham R. , Choudhary Jyoti S. , Wilkinson J. Mark , Zeggini Eleftheria
Published: February 2021

Osteoarthritis causes pain and functional disability for over 500 million people worldwide. To develop disease-stratifying tools and modifying therapies, we need a better understanding of the molecular basis of the disease in relevant tissue and cell types. Here, we study primary cartilage and synovium from 115 patients with osteoarthritis to construct a deep molecular signature map of the disease. By integrating genetics with transcriptomics and proteomics, we discover molecular trait loci in each tissue type and omics level, identify likely effector genes for osteoarthritis-associated genetic signals and highlight high-value targets for drug development and repurposing. These findings provide insights into disease aetiopathology, and offer translational opportunities in response to the global clinical challenge of osteoarthritis.
METTL3-dependent m6A modification programs T follicular helper cell differentiation
Authors: Yao Yingpeng , Yang Ying , Guo Wenhui , Xu Lifan , You Menghao , Zhang Yi-Chang , Sun Zhen , Cui Xiao , Yu Guotao , Qi Zhihong , Liu Jingjing , Wang Fang , Liu Juanjuan , Zhao Tianyan , Ye Lilin , Yang Yun-Gui , Yu Shuyang
Published: February 2021

T follicular helper (TFH) cells are specialized effector CD4+ T cells critical to humoral immunity. Whether post-transcriptional regulation has a function in TFH cells is unknown. Here, we show conditional deletion of METTL3 (a methyltransferase catalyzing mRNA N6-methyladenosine (m6A) modification) in CD4+ T cells impairs TFH differentiation and germinal center responses in a cell-intrinsic manner in mice. METTL3 is necessary for expression of important TFH signature genes, including Tcf7, Bcl6, Icos and Cxcr5 and these effects depend on intact methyltransferase activity. m6A-miCLIP-seq shows the 3′ UTR of Tcf7 mRNA is subjected to METTL3-dependent m6A modification. Loss of METTL3 or mutation of the Tcf7 3′ UTR m6A site results in accelerated decay of Tcf7 transcripts. Importantly, ectopic expression of TCF-1 (encoded by Tcf7) rectifies TFH defects owing to METTL3 deficiency. Our findings indicate that METTL3 stabilizes Tcf7 transcripts via m6A modification to ensure activation of a TFH transcriptional program, indicating a pivotal function of post-transcriptional regulation in promoting TFH cell differentiation.
Nanoengineered chiral Pt-Ir alloys for high-performance enantioselective electrosynthesis
Authors: Butcha Sopon , Assavapanumat Sunpet , Ittisanronnachai Somlak , Lapeyre Veronique , Wattanakit Chularat , Kuhn Alexander
Published: February 2021

The design of efficient chiral catalysts is of crucial importance since it allows generating enantiomerically pure compounds. Tremendous efforts have been made over the past decades regarding the development of materials with enantioselective properties for various potential applications ranging from sensing to catalysis and separation. Recently, chiral features have been generated in mesoporous metals. Although these monometallic matrices show interesting enantioselectivity, they suffer from rather low stability, constituting an important roadblock for applications. Here, a straightforward strategy to circumvent this limitation by using nanostructured platinum-iridium alloys is presented. These materials can be successfully encoded with chiral information by co-electrodeposition from Pt and Ir salts in the simultaneous presence of a chiral compound and a lyotropic liquid crystal as asymmetric template and mesoporogen, respectively. The alloys enable a remarkable discrimination between chiral compounds and greatly improved enantioselectivity when used for asymmetric electrosynthesis (>95 %ee), combined with high electrochemical stability.
Retroviral integrations contribute to elevated host cancer rates during germline invasion
Authors: McEwen Gayle K. , Alquezar-Planas David E. , Dayaram Anisha , Gillett Amber , Tarlinton Rachael , Mongan Nigel , Chappell Keith J. , Henning Joerg , Tan Milton , Timms Peter , Young Paul R. , Roca Alfred L. , Greenwood Alex D.
Published: February 2021

Repeated retroviral infections of vertebrate germlines have made endogenous retroviruses ubiquitous features of mammalian genomes. However, millions of years of evolution obscure many of the immediate repercussions of retroviral endogenisation on host health. Here we examine retroviral endogenisation during its earliest stages in the koala (Phascolarctos cinereus), a species undergoing germline invasion by koala retrovirus (KoRV) and affected by high cancer prevalence. We characterise KoRV integration sites (IS) in tumour and healthy tissues from 10 koalas, detecting 1002 unique IS, with hotspots of integration occurring in the vicinity of known cancer genes. We find that tumours accumulate novel IS, with proximate genes over-represented for cancer associations. We detect dysregulation of genes containing IS and identify a highly-expressed transduced oncogene. Our data provide insights into the tremendous mutational load suffered by the host during active retroviral germline invasion, a process repeatedly experienced and overcome during the evolution of vertebrate lineages.
Ultracold atom interferometry in space
Authors: Lachmann Maike D. , Ahlers Holger , Becker Dennis , Dinkelaker Aline N. , Grosse Jens , Hellmig Ortwin , Müntinga Hauke , Schkolnik Vladimir , Seidel Stephan T. , Wendrich Thijs , Wenzlawski André , Carrick Benjamin , Gaaloul Naceur , Lüdtke Daniel , Braxmaier Claus , Ertmer Wolfgang , Krutzik Markus , Lämmerzahl Claus , Peters Achim , Schleich Wolfgang P. , Sengstock Klaus , Wicht Andreas , Windpassinger Patrick , Rasel Ernst M.
Published: February 2021

Bose-Einstein condensates (BECs) in free fall constitute a promising source for space-borne interferometry. Indeed, BECs enjoy a slowly expanding wave function, display a large spatial coherence and can be engineered and probed by optical techniques. Here we explore matter-wave fringes of multiple spinor components of a BEC released in free fall employing light-pulses to drive Bragg processes and induce phase imprinting on a sounding rocket. The prevailing microgravity played a crucial role in the observation of these interferences which not only reveal the spatial coherence of the condensates but also allow us to measure differential forces. Our work marks the beginning of matter-wave interferometry in space with future applications in fundamental physics, navigation and earth observation.
Oscillations of Delta-like1 regulate the balance between differentiation and maintenance of muscle stem cells
Authors: Zhang Yao , Lahmann Ines , Baum Katharina , Shimojo Hiromi , Mourikis Philippos , Wolf Jana , Kageyama Ryoichiro , Birchmeier Carmen
Published: February 2021

Cell-cell interactions mediated by Notch are critical for the maintenance of skeletal muscle stem cells. However, dynamics, cellular source and identity of functional Notch ligands during expansion of the stem cell pool in muscle growth and regeneration remain poorly characterized. Here we demonstrate that oscillating Delta-like 1 (Dll1) produced by myogenic cells is an indispensable Notch ligand for self-renewal of muscle stem cells in mice. Dll1 expression is controlled by the Notch target Hes1 and the muscle regulatory factor MyoD. Consistent with our mathematical model, our experimental analyses show that Hes1 acts as the oscillatory pacemaker, whereas MyoD regulates robust Dll1 expression. Interfering with Dll1 oscillations without changing its overall expression level impairs self-renewal, resulting in premature differentiation of muscle stem cells during muscle growth and regeneration. We conclude that the oscillatory Dll1 input into Notch signaling ensures the equilibrium between self-renewal and differentiation in myogenic cell communities.
VPS34 K29/K48 branched ubiquitination governed by UBE3C and TRABID regulates autophagy, proteostasis and liver metabolism
Authors: Chen Yu-Hsuan , Huang Tzu-Yu , Lin Yu-Tung , Lin Shu-Yu , Li Wen-Hsin , Hsiao Hsiang-Jung , Yan Ruei-Liang , Tang Hong-Wen , Shen Zhao-Qing , Chen Guang-Chao , Wu Kuen-Phon , Tsai Ting-Fen , Chen Ruey-Hwa
Published: February 2021

The ubiquitin–proteasome system (UPS) and autophagy are two major quality control processes whose impairment is linked to a wide variety of diseases. The coordination between UPS and autophagy remains incompletely understood. Here, we show that ubiquitin ligase UBE3C and deubiquitinating enzyme TRABID reciprocally regulate K29/K48-branched ubiquitination of VPS34. We find that this ubiquitination enhances the binding of VPS34 to proteasomes for degradation, thereby suppressing autophagosome formation and maturation. Under ER and proteotoxic stresses, UBE3C recruitment to phagophores is compromised with a concomitant increase of its association with proteasomes. This switch attenuates the action of UBE3C on VPS34, thereby elevating autophagy activity to facilitate proteostasis, ER quality control and cell survival. Specifically in the liver, we show that TRABID-mediated VPS34 stabilization is critical for lipid metabolism and is downregulated during the pathogenesis of steatosis. This study identifies a ubiquitination type on VPS34 and elucidates its cellular fate and physiological functions in proteostasis and liver metabolism.
The atomistic details of the ice recrystallisation inhibition activity of PVA
Authors: Bachtiger Fabienne , Congdon Thomas R. , Stubbs Christopher , Gibson Matthew I. , Sosso Gabriele C.
Published: February 2021

Understanding the ice recrystallisation inhibition (IRI) activity of antifreeze biomimetics is crucial to the development of the next generation of cryoprotectants. In this work, we bring together molecular dynamics simulations and quantitative experimental measurements to unravel the microscopic origins of the IRI activity of poly(vinyl)alcohol (PVA)—the most potent of biomimetic IRI agents. Contrary to the emerging consensus, we find that PVA does not require a “lattice matching” to ice in order to display IRI activity: instead, it is the effective volume of PVA and its contact area with the ice surface which dictates its IRI strength. We also find that entropic contributions may play a role in the ice-PVA interaction and we demonstrate that small block co-polymers (up to now thought to be IRI-inactive) might display significant IRI potential. This work clarifies the atomistic details of the IRI activity of PVA and provides novel guidelines for the rational design of cryoprotectants.
Experimental demonstration of entanglement-enabled universal quantum cloning in a circuit
Authors: Yang Zhen-Biao , Han Pei-Rong , Huang Xin-Jie , Ning Wen , Li Hekang , Xu Kai , Zheng Dongning , Fan Heng , Zheng Shi-Biao
Published: February 2021

No-cloning theorem forbids perfect cloning of an unknown quantum state. A universal quantum cloning machine (UQCM), capable of producing two copies of any input qubit with the optimal fidelity, is of fundamental interest and has applications in quantum information processing. This is enabled by delicately tailored nonclassical correlations between the input qubit and the copying qubits, which distinguish the UQCM from a classical counterpart, but whose experimental demonstrations are still lacking. We here implement the UQCM in a superconducting circuit and investigate these correlations. The measured entanglements well agree with our theoretical prediction that they are independent of the input state and thus constitute a universal quantum behavior of the UQCM that was not previously revealed. Another feature of our experiment is the realization of deterministic and individual cloning, in contrast to previously demonstrated UQCMs, which either were probabilistic or did not constitute true cloning of individual qubits.
DNA hydrolysing IgG catalytic antibodies: an emerging link between psychoses and autoimmunity
Authors: Ramesh Rajendran , Sundaresh Aparna , Rajkumar Ravi Philip , Negi Vir Singh , Vijayalakshmi M. A. , Krishnamoorthy Rajagopal , Tamouza Ryad , Leboyer Marion , Kamalanathan A. S.
Published: February 2021

It is not uncommon to observe autoimmune comorbidities in a significant subset of patients with psychotic disorders, namely schizophrenia (SCZ) and bipolar disorder (BPD). To understand the autoimmune basis, the DNA abyzme activity mediated by serum polyclonal IgG Abs were examined in psychoses patients, quantitatively, by an in-house optimized DNase assay. A similar activity exhibited by IgG Abs from neuropsychiatric-systemic lupus erythematosus (NP-SLE) patients was used as a comparator. Our data revealed that the IgG DNase activity of SCZ was close to that of NP-SLE and it was twofold higher than the healthy controls. Interestingly, the association between DNase activity with PANSS (positive, general and total scores) and MADRS were noted in a subgroup of SCZ and BPD patients, respectively. In our study group, the levels of IL-6 and total IgG in BPD patients were higher than SCZ and healthy controls, indicating a relatively inflammatory nature in BPD, while autoimmune comorbidity was mainly observed in SCZ patients.
Highly pathogenic avian influenza A/Guangdong/17SF003/2016 is immunogenic and induces cross-protection against antigenically divergent H7N9 viruses
Authors: Radvak Peter , Kosikova Martina , Kuo Yuan-Chia , Li Xing , Garner Richard , Schmeisser Falko , Kosik Ivan , Ye Zhiping , Weir Jerry P. , Yewdell Jonathan W. , Xie Hang
Published: February 2021

Avian influenza A(H7N9) epidemics have a fatality rate of approximately 40%. Previous studies reported that low pathogenic avian influenza (LPAI)-derived candidate vaccine viruses (CVVs) are poorly immunogenic. Here, we assess the immunogenicity and efficacy of a highly pathogenic avian influenza (HPAI) A/Guangdong/17SF003/2016 (GD/16)-extracted hemagglutinin (eHA) vaccine. GD/16 eHA induces robust H7-specific antibody responses in mice with a marked adjuvant antigen-sparing effect. Mice immunized with adjuvanted GD/16 eHA are protected from the lethal LPAI and HPAI H7N9 challenges, in stark contrast to low antibody titers and high mortality in mice receiving adjuvanted LPAI H7 eHAs. The protection correlates well with the magnitude of the H7-specific antibody response (IgG and microneutralization) or HA group 2 stem-specific IgG. Inclusion of adjuvanted GD/16 eHA in heterologous prime-boost improves the immunogenicity and protection of LPAI H7 HAs in mice. Our findings support the inclusion of GD/16-derived CVV in the pandemic preparedness vaccine stockpile.
High-resolution surface faulting from the 1983 Idaho Lost River Fault Mw 6.9 earthquake and previous events
Authors: Bello Simone , Scott Chelsea P. , Ferrarini Federica , Brozzetti Francesco , Scott Tyler , Cirillo Daniele , de Nardis Rita , Arrowsmith J Ramón , Lavecchia Giusy
Published: February 2021

We present high-resolution mapping and surface faulting measurements along the Lost River fault (Idaho-USA), a normal fault activated in the 1983 (Mw6.9) earthquake. The earthquake ruptured ~35 km of the fault with a maximum throw of ~3 m. From new 5 to 30 cm-pixel resolution topography collected by an Unmanned Aerial Vehicle, we produce the most comprehensive dataset of systematically measured vertical separations from ~37 km of fault length activated by the 1983 and prehistoric earthquakes. We provide Digital Elevation Models, orthophotographs, and three tables of: (i) 757 surface rupture traces, (ii) 1295 serial topographic profiles spaced 25 m apart that indicate rupture zone width and (iii) 2053 vertical separation measurements, each with additional textual and numerical fields. Our novel dataset supports advancing scientific knowledge about this fault system, refining scaling laws of intra-continental faults, comparing to other earthquakes to better understand faulting processes, and contributing to global probabilistic hazard approaches. Our methodology can be applied to other fault zones with high-resolution topographic data.
Replicability of neural responses to speech accent is driven by study design and analytical parameters
Authors: Strauber C. Benjamin , Ali Lestat R. , Fujioka Takako , Thille Candace , McCandliss Bruce D.
Published: February 2021

Recent studies have reported evidence that listeners' brains process meaning differently in speech with an in-group as compared to an out-group accent. However, among studies that have used electroencephalography (EEG) to examine neural correlates of semantic processing of speech in different accents, the details of findings are often in conflict, potentially reflecting critical variations in experimental design and/or data analysis parameters. To determine which of these factors might be driving inconsistencies in results across studies, we systematically investigate how analysis parameter sets from several of these studies impact results obtained from our own EEG data set. Data were collected from forty-nine monolingual North American English listeners in an event-related potential (ERP) paradigm as they listened to semantically congruent and incongruent sentences spoken in an American accent and an Indian accent. Several key effects of in-group as compared to out-group accent were robust across the range of parameters found in the literature, including more negative scalp-wide responses to incongruence in the N400 range, more positive posterior responses to congruence in the N400 range, and more positive posterior responses to incongruence in the P600 range. These findings, however, are not fully consistent with the reported observations of the studies whose parameters we used, indicating variation in experimental design may be at play. Other reported effects only emerged under a subset of the analytical parameters tested, suggesting that analytical parameters also drive differences. We hope this spurs discussion of analytical parameters and investigation of the contributions of individual study design variables in this growing field.
Investigation of biological activity of soil fungal extracts and LC/MS-QTOF based metabolite profiling
Authors: Mohammed Afrah E. , Sonbol Hana , Alwakeel Suaad Saleh , Alotaibi Modhi O. , Alotaibi Sohailah , Alothman Nouf , Suliman Rasha Saad , Ahmedah Hanadi Talal , Ali Rizwan
Published: February 2021

Soil is considered an extensively explored ecological niche for microorganisms that produce useful biologically active natural products suitable for pharmaceutical applications. The current study aimed at investigating biological activities and metabolic profiles of three fungal strains identified from different desert sites in Saudi Arabia. Soil fungal isolates were collected from AlQasab, Tabuk, and Almuzahimiyah in Saudi Arabia and identified. Furthermore, their antibacterial activity was investigated against Staphylococcus aureus, Enterococcus faecalis, Klebsiella pneumonia, and Escherichia coli in blood, nutrient, and Sabouraud dextrose agars. Moreover, fungal extracts were evaluated on cell viability/proliferation against human breast carcinoma and colorectal adenocarcinoma cells. To identify the biomolecules of the fungal extracts, High-performance liquid chromatography HPLC–DAD coupled to analytical LC–QTOF-MS method was employed for fungal ethyl acetate crude extract. Identified fungal isolates, Chaetomium sp. Bipolaris sp. and Fusarium venenatum showed varied inhibitory activity against tested microbes in relation to crude extract, microbial strain tested, and growth media. F. venenatum showed higher anticancer activity compared to Chaetomium sp. and Bipolaris sp. extracts against four of the tested cancer cell lines. Screening by HPLC and LC/MS-QTOF identified nine compounds from Chaetomium sp. and three from Bipolaris sp. however, for F. venenatum extracts compounds were not fully identified. In light of the present findings, some biological activities of fungal extracts were approved in vitro, suggesting that such extracts could be a useful starting point to find compounds that possess promising agents for medical applications. Further investigations to identify exact biomolecules from F. venenatum extracts are needed.
Insight into the surface activity of defect structure in α-MnO2 nanorod: first-principles research
Authors: Zhao Pengsen , Li Guifa , Zheng Haizhong , Lu Shiqiang , Peng Ping
Published: February 2021

The contribution of defect structure to the catalytic property of α-MnO2 nanorod still keeps mysterious right now. Using microfacet models representing defect structure and bulk models with high Miller index, several parameters, such as cohesive energy, surface energy, density of state, electrostatic potential, et al., have been used to investigate the internal mechanism of their chemical activities by first-principles calculation. The results show that the trend in surface energies of microfacet models follows as Esurface[(112 × 211)] > Esurface[(110 × 211)] > Esurface[(100 × 211)] > Esurface[(111 × 211)] > Esurface[(112 × 112)] > Esurface[(111 × 112)], wherein all of them are larger than that of bulk models. So the chemical activity of defect structure is much more powerful than that of bulk surface. Deep researches on electronic structure show that the excellent chemical activity of microfacet structure has larger value in dipole moments and electrostatic potential than that of bulk surface layer. And the microfacet models possess much more peaks of valent electrons in deformantion electronic density and molecular orbital. Density of state indicates that the excellent chemical activity of defect structure comes from their proper hybridization in p and d orbitals.
Native and invasive ants affect floral visits of pollinating honey bees in pumpkin flowers (Cucurbita maxima)
Authors: Unni Anjana Pisharody , Mir Sajad Hussain , Rajesh T. P. , Ballullaya U. Prashanth , Jose Thomas , Sinu Palatty Allesh
Published: February 2021

Global pollinator decline is a major concern. Several factors—climate change, land-use change, the reduction of flowers, pesticide use, and invasive species—have been suggested as the reasons. Despite being a potential reason, the effect of ants on flowers received less attention. The consequences of ants being attracted to nectar sources in plants vary depending upon factors like the nectar source's position, ants' identity, and other mutualists interacting with the plants. We studied the interaction between flower-visiting ants and pollinators in Cucurbita maxima and compared the competition exerted by native and invasive ants on its pollinators to examine the hypothesis that the invasive ants exacerbate more interference competition to pollinators than the native ants. We assessed the pollinator's choice, visitation rate, and time spent/visit on the flowers. Regardless of species and nativity, ants negatively influenced all the pollinator visitation traits, such as visitation rate and duration spent on flowers. The invasive ants exerted a higher interference competition on the pollinators than the native ants did. Despite performing pollination in flowers with generalist pollination syndrome, ants can threaten plant-pollinator mutualism in specialist plants like monoecious plants. A better understanding of factors influencing pollination will help in implementing better management practices.
Development and validation of a real-time PCR assay to detect Cannabis sativa in food
Authors: Weck Sandra , Peterseil Verena , Mayer Helmut K. , Hochegger Rupert
Published: February 2021

Regarding the prospective investigation of food authenticity and adulteration the aim of the present study was the development and validation of a real-time PCR assay to identify hemp (Cannabis sativa) which has gained increasing importance as a valuable food ingredient. The assay targets a specific spacer DNA sequence in Cannabis sativa chloroplasts and detects 1.5 pg hemp DNA, which is equivalent to 18 copies/µL. Corresponding to the very low LOD (0.00031 ng/µL) the method allows the detection of hemp even in the infinitesimal concentration of contaminants. Due to a SNP in position 603, hemp can be identified unequivocally and discriminated from its closest relative hops (Humulus lupulus). The PCR method shows no cross-reactivity with 39 of 46 tested plant species. Low cross-reactivity with mulberry, stinging nettle, lavender, cornflower, wine, figs and hops can be neglected, because the Δ Ct-values are > 14, and the obtained Ct-values are beyond the cut-off for a positive assessment (Ct-values ≤ 33). Moreover, the suitability of the method to identify hemp as a food ingredient was proved by analysing diverse food products such as chocolate or cookies.
The σ54 system directly regulates bacterial natural product genes
Authors: Ma Muqing , Welch Roy D. , Garza Anthony G.
Published: February 2021

Bacterial-derived polyketide and non-ribosomal peptide natural products are crucial sources of therapeutics and yet little is known about the conditions that favor activation of natural product genes or the regulatory machinery controlling their transcription. Recent findings suggest that the σ54 system, which includes σ54-loaded RNA polymerase and transcriptional activators called enhancer binding proteins (EBPs), might be a common regulator of natural product genes. Here, we explored this idea by analyzing a selected group of putative σ54 promoters identified in Myxococcus xanthus natural product gene clusters. We show that mutations in putative σ54-RNA polymerase binding regions and in putative Nla28 EBP binding sites dramatically reduce in vivo promoter activities in growing and developing cells. We also show in vivo promoter activities are reduced in a nla28 mutant, that Nla28 binds to wild-type fragments of these promoters in vitro, and that in vitro binding is lost when the Nla28 binding sites are mutated. Together, our results indicate that M. xanthus uses σ54 promoters for transcription of at least some of its natural product genes. Interestingly, the vast majority of experimentally confirmed and putative σ54 promoters in M. xanthus natural product loci are located within genes and not in intergenic sequences.
Diversity of Avian leukosis virus subgroup J in local chickens, Jiangxi, China
Authors: Li Haiqin , Tan Meifang , Zhang Fanfan , Ji Huayuan , Zeng Yanbing , Yang Qun , Tan Jia , Huang Jiangnan , Su Qi , Huang Yu , Kang Zhaofeng
Published: February 2021

Avian leukosis caused by avian leukosis virus (ALV) is one of the most severe diseases endangering the poultry industry. When the eradication measures performed in commercial broilers and layers have achieved excellent results, ALV in some local chickens has gradually attracted attention. Since late 2018, following the re-outbreak of ALV-J in white feather broilers in China, AL-like symptoms also suddenly broke out in some local flocks, leading to great economic losses. In this study, a systematic epidemiological survey was carried out in eight local chicken flocks in Jiangxi Province, China, and 71 strains were finally isolated from 560 samples, with the env sequences of them being successfully sequenced. All of those new isolates belong to subgroup J but they have different molecular features and were very different from the strains that emerged in white feature broilers recently, with some strains being highly consistent with those previously isolated from commercial broilers, layers and other flocks or even isolated from USA and Russian, suggesting these local chickens have been acted as reservoirs to accumulate various ALV-J strains for a long time. More seriously, phylogenetic analysis shows that there were also many novel strains emerging and in a separate evolutionary branch, indicating several new mutated ALVs are being bred in local chickens. Besides, ALV-J strains isolated in this study can be further divided into ten groups, while there were more or fewer groups in different chickens, revealing that ALV may cross propagate in those flocks. The above analyses explain the complex background and future evolution trend of ALV-J in Chinese local chickens, providing theoretical support for the establishment of corresponding prevention and control measures.
An immortalized porcine macrophage cell line competent for the isolation of African swine fever virus
Authors: Masujin Kentaro , Kitamura Tomoya , Kameyama Ken -ichiro , Okadera Kota , Nishi Tatsuya , Takenouchi Takato , Kitani Hiroshi , Kokuho Takehiro
Published: February 2021

African swine fever virus (ASFV) is the etiological agent of African swine fever (ASF), a fatal hemorrhagic disease of domestic pigs and wild boar. The virus primarily infects macrophage and monocyte host cells, these do not grow in vitro. Many attempts have been made to establish sustainable ASFV-sensitive cell lines, but which supported only low viral replication levels of limited, mostly artificially attenuated strains of ASFV. Here, we examined the competence of a novel cell line of immortalized porcine kidney macrophages (IPKM) for ASFV infection. We demonstrated that IPKM cells can facilitate high levels (> 107.0 TCID50/mL) of viral replication of ASFV, and hemadsorption reactions and cytopathic effects were observed as with porcine alveolar macrophages when inoculated with virulent field isolates: Armenia07, Kenya05/Tk-1, and Espana75. These results suggested that IPKM may be a valuable tool for the isolation, replication, and genetic manipulation of ASFV in both basic and applied ASF research.
Prediction accuracy of standard and total keratometry by swept-source optical biometer for multifocal intraocular lens power calculation
Authors: Lee Hun , Chung Jae Lim , Kim Young Jun , Kim Jae Yong , Tchah Hungwon
Published: February 2021

We aimed to compare the refractive outcomes of cataract surgery with diffractive multifocal intraocular lenses (IOLs) using standard keratometry (K) and total keratometry (TK). In this retrospective observational case series study, a total of 302 patients who underwent cataract surgery with multifocal IOL implantation were included. Predicted refractive outcomes were calculated based on the current standard formulas and a new formula developed for TK using K and TK, which were obtained from a swept-source optical biometer. At 2-month postoperatively, median absolute prediction errors (MedAEs) and proportion of eyes within ± 0.50 diopters (D) of predicted postoperative spherical equivalent (SE) refraction were analyzed. There was no significant difference between MedAEs or proportion of eyes within ± 0.50D of predicted refraction from K and TK in each formula. In TFNT00 and 839MP IOL cases, there was no difference between MedAEs from K and TK using any formula. In 829MP IOL cases, MedAE from TK was significantly larger than that from K in Barrett Universal II/Barrett TK Universal II (P = 0.033). In 677MY IOL cases, MedAE from TK was significantly larger than that from K in Haigis (P = 0.020) and Holladay 2 (P = 0.006) formulas. In the subgroup analysis for IOL, there was no difference between the proportion of eyes within ± 0.50 D of predicted refraction from K and TK using any formula. TFNT00 and 839MP IOLs were favorable with TK, with 677MY IOL with K and 829MP IOL being in a neutral position, which necessitates the study that investigates the accuracy of the new TK technology.
Homologies between SARS-CoV-2 and allergen proteins may direct T cell-mediated heterologous immune responses
Authors: Balz Kathrin , Kaushik Abhinav , Chen Meng , Cemic Franz , Heger Vanessa , Renz Harald , Nadeau Kari , Skevaki Chrysanthi
Published: February 2021

The outbreak of the new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a public health emergency. Asthma does not represent a risk factor for COVID-19 in several published cohorts. We hypothesized that the SARS-CoV-2 proteome contains T cell epitopes, which are potentially cross-reactive to allergen epitopes. We aimed at identifying homologous peptide sequences by means of two distinct complementary bioinformatics approaches. Pipeline 1 included prediction of MHC Class I and Class II epitopes contained in the SARS-CoV-2 proteome and allergens along with alignment and elaborate ranking approaches. Pipeline 2 involved alignment of SARS-CoV-2 overlapping peptides with known allergen-derived T cell epitopes. Our results indicate a large number of MHC Class I epitope pairs including known as well as de novo predicted allergen T cell epitopes with high probability for cross-reactivity. Allergen sources, such as Aspergillus fumigatus, Phleum pratense and Dermatophagoides species are of particular interest due to their association with multiple cross-reactive candidate peptides, independently of the applied bioinformatic approach. In contrast, peptides derived from food allergens, as well as MHC class II epitopes did not achieve high in silico ranking and were therefore not further investigated. Our findings warrant further experimental confirmation along with examination of the functional importance of such cross-reactive responses.
An alternative food source for metabolism and longevity studies in Caenorhabditis elegans
Authors: Beydoun Safa , Choi Hyo Sub , Dela-Cruz Gabrielle , Kruempel Joseph , Huang Shijiao , Bazopoulou Daphne , Miller Hillary A. , Schaller Megan L. , Evans Charles R. , Leiser Scott F.
Published: February 2021

Caenorhabditis elegans is an instrumental research model used to advance our knowledge in areas including development, metabolism, and aging. However, research on metabolism and/or other measures of health/aging are confounded by the nematode’s food source in the lab, live E. coli bacteria. Commonly used treatments, including ultraviolet irradiation and antibiotics, are successful in preventing bacterial replication, but the bacteria can remain metabolically active. The purpose of this study is to develop a metabolically inactive food source for the worms that will allow us to minimize the confounding effects of bacterial metabolism on worm metabolism and aging. Our strategy is to use a paraformaldehyde (PFA) treated E. coli food source and to determine its effects on worm health, metabolism and longevity. We initially determine the lowest possible concentrations of PFA necessary to rapidly and reproducibly kill bacteria. We then measure various aspects of worm behavior, healthspan and longevity, including growth rate, food attraction, brood size, lifespan and metabolic assessments, such as oxygen consumption and metabolomics. Our resulting data show that worms eat and grow well on these bacteria and support the use of 0.5% PFA-killed bacteria as a nematode food source for metabolic, drug, and longevity experiments.
The cancer glycocalyx mediates intravascular adhesion and extravasation during metastatic dissemination
Authors: Offeddu Giovanni S. , Hajal Cynthia , Foley Colleen R. , Wan Zhengpeng , Ibrahim Lina , Coughlin Mark F. , Kamm Roger D.
Published: February 2021

The glycocalyx on tumor cells has been recently identified as an important driver for cancer progression, possibly providing critical opportunities for treatment. Metastasis, in particular, is often the limiting step in the survival to cancer, yet our understanding of how tumor cells escape the vascular system to initiate metastatic sites remains limited. Using an in vitro model of the human microvasculature, we assess here the importance of the tumor and vascular glycocalyces during tumor cell extravasation. Through selective manipulation of individual components of the glycocalyx, we reveal a mechanism whereby tumor cells prepare an adhesive vascular niche by depositing components of the glycocalyx along the endothelium. Accumulated hyaluronic acid shed by tumor cells subsequently mediates adhesion to the endothelium via the glycoprotein CD44. Trans-endothelial migration and invasion into the stroma occurs through binding of the isoform CD44v to components of the sub-endothelial extra-cellular matrix. Targeting of the hyaluronic acid-CD44 glycocalyx complex results in significant reduction in the extravasation of tumor cells. These studies provide evidence of tumor cells repurposing the glycocalyx to promote adhesive interactions leading to cancer progression. Such glycocalyx-mediated mechanisms may be therapeutically targeted to hinder metastasis and improve patient survival.