bluuebunny/crossref_metadata_2025 huggingface dataset:
USP9X-mediated KDM4C deubiquitination promotes lung cancer radioresistance by epigenetically inducing TGF-β2 transcription
Authors: Jie Xiaohua , Fong William Pat , Zhou Rui , Zhao Ye , Zhao Yingchao , Meng Rui , Zhang Sheng , Dong Xiaorong , Zhang Tao , Yang Kunyu , Wu Gang , Xu Shuangbing
Published: February 2021

Radioresistance is regarded as the main barrier to effective radiotherapy in lung cancer. However, the underlying mechanisms of radioresistance remain elusive. Here, we show that lysine-specific demethylase 4C (KDM4C) is overexpressed and correlated with poor prognosis in lung cancer patients. We provide evidence that genetical or pharmacological inhibition of KDM4C impairs tumorigenesis and radioresistance in lung cancer in vitro and in vivo. Moreover, we uncover that KDM4C upregulates TGF-β2 expression by directly reducing H3K9me3 level at the TGF-β2 promoter and then activates Smad/ATM/Chk2 signaling to confer radioresistance in lung cancer. Using tandem affinity purification technology, we further identify deubiquitinase USP9X as a critical binding partner that deubiquitinates and stabilizes KDM4C. More importantly, depletion of USP9X impairs TGF-β2/Smad signaling and radioresistance by destabilizing KDM4C in lung cancer cells. Thus, our findings demonstrate that USP9X-mediated KDM4C deubiquitination activates TGF-β2/Smad signaling to promote radioresistance, suggesting that targeting KDM4C may be a promising radiosensitization strategy in the treatment of lung cancer.
Dynamically remodeled hepatic extracellular matrix predicts prognosis of early-stage cirrhosis
Authors: Wu Yuexin , Cao Yuyan , Xu Keren , Zhu Yue , Qiao Yuemei , Wu Yanjun , Chen Jianfeng , Li Chen , Zeng Rong , Ge Gaoxiang
Published: February 2021

Liver cirrhosis remains major health problem. Despite the progress in diagnosis of asymptomatic early-stage cirrhosis, prognostic biomarkers are needed to identify cirrhotic patients at high risk developing advanced stage disease. Liver cirrhosis is the result of deregulated wound healing and is featured by aberrant extracellular matrix (ECM) remodeling. However, it is not comprehensively understood how ECM is dynamically remodeled in the progressive development of liver cirrhosis. It is yet unknown whether ECM signature is of predictive value in determining prognosis of early-stage liver cirrhosis. In this study, we systematically analyzed proteomics of decellularized hepatic matrix and identified four unique clusters of ECM proteins at tissue damage/inflammation, transitional ECM remodeling or fibrogenesis stage in carbon tetrachloride-induced liver fibrosis. In particular, basement membrane (BM) was heavily deposited at the fibrogenesis stage. BM component minor type IV collagen α5 chain expression was increased in activated hepatic stellate cells. Knockout of minor type IV collagen α5 chain ameliorated liver fibrosis by hampering hepatic stellate cell activation and promoting hepatocyte proliferation. ECM signatures were differentially enriched in the biopsies of good and poor prognosis early-stage liver cirrhosis patients. Clusters of ECM proteins responsible for homeostatic remodeling and tissue fibrogenesis, as well as basement membrane signature were significantly associated with disease progression and patient survival. In particular, a 14-gene signature consisting of basement membrane proteins is potent in predicting disease progression and patient survival. Thus, the ECM signatures are potential prognostic biomarkers to identify cirrhotic patients at high risk developing advanced stage disease.
Listeners’ perceptions of the certainty and honesty of a speaker are associated with a common prosodic signature
Authors: Goupil Louise , Ponsot Emmanuel , Richardson Daniel , Reyes Gabriel , Aucouturier Jean-Julien
Published: February 2021

The success of human cooperation crucially depends on mechanisms enabling individuals to detect unreliability in their conspecifics. Yet, how such epistemic vigilance is achieved from naturalistic sensory inputs remains unclear. Here we show that listeners’ perceptions of the certainty and honesty of other speakers from their speech are based on a common prosodic signature. Using a data-driven method, we separately decode the prosodic features driving listeners’ perceptions of a speaker’s certainty and honesty across pitch, duration and loudness. We find that these two kinds of judgments rely on a common prosodic signature that is perceived independently from individuals’ conceptual knowledge and native language. Finally, we show that listeners extract this prosodic signature automatically, and that this impacts the way they memorize spoken words. These findings shed light on a unique auditory adaptation that enables human listeners to quickly detect and react to unreliability during linguistic interactions.
Droplet printing reveals the importance of micron-scale structure for bacterial ecology
Authors: Krishna Kumar Ravinash , Meiller-Legrand Thomas A. , Alcinesio Alessandro , Gonzalez Diego , Mavridou Despoina A. I. , Meacock Oliver J. , Smith William P. J. , Zhou Linna , Kim Wook , Pulcu Gökçe Su , Bayley Hagan , Foster Kevin R.
Published: February 2021

Bacteria often live in diverse communities where the spatial arrangement of strains and species is considered critical for their ecology. However, a test of this hypothesis requires manipulation at the fine scales at which spatial structure naturally occurs. Here we develop a droplet-based printing method to arrange bacterial genotypes across a sub-millimetre array. We print strains of the gut bacterium Escherichia coli that naturally compete with one another using protein toxins. Our experiments reveal that toxin-producing strains largely eliminate susceptible non-producers when genotypes are well-mixed. However, printing strains side-by-side creates an ecological refuge where susceptible strains can persist in large numbers. Moving to competitions between toxin producers reveals that spatial structure can make the difference between one strain winning and mutual destruction. Finally, we print different potential barriers between competing strains to understand how ecological refuges form, which shows that cells closest to a toxin producer mop up the toxin and protect their clonemates. Our work provides a method to generate customised bacterial communities with defined spatial distributions, and reveals that micron-scale changes in these distributions can drive major shifts in ecology.
Single-molecule force spectroscopy reveals the dynamic strength of the hair-cell tip-link connection
Authors: Mulhall Eric M. , Ward Andrew , Yang Darren , Koussa Mounir A. , Corey David P. , Wong Wesley P.
Published: February 2021

The conversion of auditory and vestibular stimuli into electrical signals is initiated by force transmitted to a mechanotransduction channel through the tip link, a double stranded protein filament held together by two adhesion bonds in the middle. Although thought to form a relatively static structure, the dynamics of the tip-link connection has not been measured. Here, we biophysically characterize the strength of the tip-link connection at single-molecule resolution. We show that a single tip-link bond is more mechanically stable relative to classic cadherins, and our data indicate that the double stranded tip-link connection is stabilized by single strand rebinding facilitated by strong cis-dimerization domains. The measured lifetime of seconds suggests the tip-link is far more dynamic than previously thought. We also show how Ca2+ alters tip-link lifetime through elastic modulation and reveal the mechanical phenotype of a hereditary deafness mutation. Together, these data show how the tip link is likely to function during mechanical stimuli.
Sequence-encoded and composition-dependent protein-RNA interactions control multiphasic condensate morphologies
Authors: Kaur Taranpreet , Raju Muralikrishna , Alshareedah Ibraheem , Davis Richoo B. , Potoyan Davit A. , Banerjee Priya R.
Published: February 2021

Multivalent protein-protein and protein-RNA interactions are the drivers of biological phase separation. Biomolecular condensates typically contain a dense network of multiple proteins and RNAs, and their competing molecular interactions play key roles in regulating the condensate composition and structure. Employing a ternary system comprising of a prion-like polypeptide (PLP), arginine-rich polypeptide (RRP), and RNA, we show that competition between the PLP and RNA for a single shared partner, the RRP, leads to RNA-induced demixing of PLP-RRP condensates into stable coexisting phases—homotypic PLP condensates and heterotypic RRP-RNA condensates. The morphology of these biphasic condensates (non-engulfing/ partial engulfing/ complete engulfing) is determined by the RNA-to-RRP stoichiometry and the hierarchy of intermolecular interactions, providing a glimpse of the broad range of multiphasic patterns that are accessible to these condensates. Our findings provide a minimal set of physical rules that govern the composition and spatial organization of multicomponent and multiphasic biomolecular condensates.
Effects of individual base-pairs on in vivo target search and destruction kinetics of bacterial small RNA
Authors: Poddar Anustup , Azam Muhammad S. , Kayikcioglu Tunc , Bobrovskyy Maksym , Zhang Jichuan , Ma Xiangqian , Labhsetwar Piyush , Fei Jingyi , Singh Digvijay , Luthey-Schulten Zaida , Vanderpool Carin K. , Ha Taekjip
Published: February 2021

Base-pairing interactions mediate many intermolecular target recognition events. Even a single base-pair mismatch can cause a substantial difference in activity but how such changes influence the target search kinetics in vivo is unknown. Here, we use high-throughput sequencing and quantitative super-resolution imaging to probe the mutants of bacterial small RNA, SgrS, and their regulation of ptsG mRNA target. Mutations that disrupt binding of a chaperone protein, Hfq, and are distal to the mRNA annealing region still decrease the rate of target association, kon, and increase the dissociation rate, koff, showing that Hfq directly facilitates sRNA–mRNA annealing in vivo. Single base-pair mismatches in the annealing region reduce kon by 24–31% and increase koff by 14–25%, extending the time it takes to find and destroy the target by about a third. The effects of disrupting contiguous base-pairing are much more modest than that expected from thermodynamics, suggesting that Hfq buffers base-pair disruptions.
Individualized interactomes for network-based precision medicine in hypertrophic cardiomyopathy with implications for other clinical pathophenotypes
Authors: Maron Bradley A. , Wang Rui-Sheng , Shevtsov Sergei , Drakos Stavros G. , Arons Elena , Wever-Pinzon Omar , Huggins Gordon S. , Samokhin Andriy O. , Oldham William M. , Aguib Yasmine , Yacoub Magdi H. , Rowin Ethan J. , Maron Barry J. , Maron Martin S. , Loscalzo Joseph
Published: February 2021

Progress in precision medicine is limited by insufficient knowledge of transcriptomic or proteomic features in involved tissues that define pathobiological differences between patients. Here, myectomy tissue from patients with obstructive hypertrophic cardiomyopathy and heart failure is analyzed using RNA-Seq, and the results are used to develop individualized protein-protein interaction networks. From this approach, hypertrophic cardiomyopathy is distinguished from dilated cardiomyopathy based on the protein-protein interaction network pattern. Within the hypertrophic cardiomyopathy cohort, the patient-specific networks are variable in complexity, and enriched for 30 endophenotypes. The cardiac Janus kinase 2-Signal Transducer and Activator of Transcription 3-collagen 4A2 (JAK2-STAT3-COL4A2) expression profile informed by the networks was able to discriminate two hypertrophic cardiomyopathy patients with extreme fibrosis phenotypes. Patient-specific network features also associate with other important hypertrophic cardiomyopathy clinical phenotypes. These proof-of-concept findings introduce personalized protein-protein interaction networks (reticulotypes) for characterizing patient-specific pathobiology, thereby offering a direct strategy for advancing precision medicine.
Biallelic loss of BCMA as a resistance mechanism to CAR T cell therapy in a patient with multiple myeloma
Authors: Samur Mehmet Kemal , Fulciniti Mariateresa , Aktas Samur Anil , Bazarbachi Abdul Hamid , Tai Yu-Tzu , Prabhala Rao , Alonso Alejandro , Sperling Adam S. , Campbell Timothy , Petrocca Fabio , Hege Kristen , Kaiser Shari , Loiseau Hervé Avet , Anderson Kenneth C. , Munshi Nikhil C.
Published: February 2021

BCMA targeting chimeric antigen receptor (CAR) T cell therapy has shown deep and durable responses in multiple myeloma. However, relapse following therapy is frequently observed, and mechanisms of resistance remain ill-defined. Here, we perform single cell genomic characterization of longitudinal samples from a patient who relapsed after initial CAR T cell treatment with lack of response to retreatment. We report selection, following initial CAR T cell infusion, of a clone with biallelic loss of BCMA acquired by deletion of one allele and a mutation that creates an early stop codon on the second allele. This loss leads to lack of CAR T cell proliferation following the second infusion and is reflected by lack of soluble BCMA in patient serum. Our analysis suggests the need for careful detection of BCMA gene alterations in multiple myeloma cells from relapse following CAR T cell therapy.
Engineering fast high-fidelity quantum operations with constrained interactions
Authors: Figueiredo Roque T. , Clerk Aashish A. , Ribeiro Hugo
Published: February 2021

Understanding how to tailor quantum dynamics to achieve the desired evolution is a crucial problem in almost all quantum technologies. Oftentimes an otherwise ideal quantum dynamics is corrupted by unavoidable interactions, and finding ways to mitigate the unwanted effects of such interactions on the dynamics is a very active field of research. Here, we present a very general method for designing high-efficiency control sequences that are fully compatible with experimental constraints on available interactions and their tunability. Our approach relies on the Magnus expansion to find order by order the necessary corrections that result in a high-fidelity operation. In the end finding, the control fields are reduced to solve a set of linear equations. We illustrate our method by applying it to a number of physically relevant problems: the strong-driving limit of a two-level system, fast squeezing in a parametrically driven cavity, the leakage problem in transmon qubit gates, and the acceleration of SNAP gates in a qubit-cavity system.
Manually curated transcriptomics data collection for toxicogenomic assessment of engineered nanomaterials
Authors: Saarimäki Laura Aliisa , Federico Antonio , Lynch Iseult , Papadiamantis Anastasios G. , Tsoumanis Andreas , Melagraki Georgia , Afantitis Antreas , Serra Angela , Greco Dario
Published: February 2021

Toxicogenomics (TGx) approaches are increasingly applied to gain insight into the possible toxicity mechanisms of engineered nanomaterials (ENMs). Omics data can be valuable to elucidate the mechanism of action of chemicals and to develop predictive models in toxicology. While vast amounts of transcriptomics data from ENM exposures have already been accumulated, a unified, easily accessible and reusable collection of transcriptomics data for ENMs is currently lacking. In an attempt to improve the FAIRness of already existing transcriptomics data for ENMs, we curated a collection of homogenized transcriptomics data from human, mouse and rat ENM exposures in vitro and in vivo including the physicochemical characteristics of the ENMs used in each study.
Genetic variation among 481 diverse soybean accessions, inferred from genomic re-sequencing
Authors: Valliyodan Babu , Brown Anne V. , Wang Juexin , Patil Gunvant , Liu Yang , Otyama Paul I. , Nelson Rex T. , Vuong Tri , Song Qijian , Musket Theresa A. , Wagner Ruth , Marri Pradeep , Reddy Sam , Sessions Allen , Wu Xiaolei , Grant David , Bayer Philipp E. , Roorkiwal Manish , Varshney Rajeev K. , Liu Xin , Edwards David , Xu Dong , Joshi Trupti , Cannon Steven B. , Nguyen Henry T.
Published: February 2021

We report characteristics of soybean genetic diversity and structure from the resequencing of 481 diverse soybean accessions, comprising 52 wild (Glycine soja) selections and 429 cultivated (Glycine max) varieties (landraces and elites). This data was used to identify 7.8 million SNPs, to predict SNP effects relative to genic regions, and to identify the genetic structure, relationships, and linkage disequilibrium. We found evidence of distinct, mostly independent selection of lineages by particular geographic location. Among cultivated varieties, we identified numerous highly conserved regions, suggesting selection during domestication. Comparisons of these accessions against the whole U.S. germplasm genotyped with the SoySNP50K iSelect BeadChip revealed that over 95% of the re-sequenced accessions have a high similarity to their SoySNP50K counterparts. Probable errors in seed source or genotype tracking were also identified in approximately 5% of the accessions.
Dynamical visualization of anisotropic electromagnetic re-emissions from a single metal micro-helix at THz frequencies
Authors: Notake T. , Iyoda T. , Arikawa T. , Tanaka K. , Otani C. , Minamide H.
Published: February 2021

The capability for actual measurements—not just simulations—of the dynamical behavior of THz electromagnetic waves, including interactions with prevalent 3D objects, has become increasingly important not only for developments of various THz devices, but also for reliable evaluation of electromagnetic compatibility. We have obtained real-time visualizations of the spatial evolution of THz electromagnetic waves interacting with a single metal micro-helix. After the micro-helix is stimulated by a broadband pico-second pulse of THz electromagnetic waves, two types of anisotropic re-emissions can occur following overall inductive current oscillations in the micro-helix. They propagate in orthogonally crossed directions with different THz frequency spectra. This unique radiative feature can be very useful for the development of a smart antenna with broadband multiplexing/demultiplexing ability and directional adaptivity. In this way, we have demonstrated that our advanced measurement techniques can lead to the development of novel functional THz devices.
China’s city-level carbon emissions during 1992–2017 based on the inter-calibration of nighttime light data
Authors: Chen Jiandong , Gao Ming , Cheng Shulei , Liu Xin , Hou Wenxuan , Song Malin , Li Ding , Fan Wei
Published: February 2021

Accurate, long-term, full-coverage carbon dioxide (CO2) data in units of prefecture-level cities are necessary for evaluations of CO2 emission reductions in China, which has become one of the world’s largest carbon-emitting countries. This study develops a novel method to match satellite-based Defense Meteorological Satellite Program’s Operational Landscan System (DMSP/OLS) and Suomi National Polar-orbiting Partnership’s Visible Infrared Imaging Radiometer Suite (NPP/VIIRS) nighttime light data, and estimates the CO2 emissions of 334 prefecture-level cities in China from 1992 to 2017. Results indicated that the eastern and coastal regions had higher carbon emissions, but their carbon intensity decreased more rapidly than other regions. Compared to previous studies, we provide the most extensive and long-term CO2 dataset to date, and these data will be of great value for further socioeconomic research. Specifically, this dataset provides a foundational data source for China’s future CO2 research and emission reduction strategies. Additionally, the methodology can be applied to other regions around the world.
Replication of HLA class II locus association with susceptibility to podoconiosis in three Ethiopian ethnic groups
Authors: Gebresilase Tewodros , Finan Chris , Suveges Daniel , Tessema Tesfaye Sisay , Aseffa Abraham , Davey Gail , Hatzikotoulas Konstantinos , Zeggini Eleftheria , Newport Melanie J. , Tekola-Ayele Fasil
Published: February 2021

Podoconiosis, a debilitating lymphoedema of the leg, results from barefoot exposure to volcanic clay soil in genetically susceptible individuals. A previous genome-wide association study (GWAS) conducted in the Wolaita ethnic group from Ethiopia showed association between single nucleotide polymorphisms (SNPs) in the HLA class II region and podoconiosis. We aimed to conduct a second GWAS in a new sample (N = 1892) collected from the Wolaita and two other Ethiopian populations, the Amhara and the Oromo, also affected by podoconiosis. Fourteen SNPs in the HLA class II region showed significant genome-wide association (P < 5.0 × 10−8) with podoconiosis. The lead SNP was rs9270911 (P = 5.51 × 10−10; OR 1.53; 95% CI 1.34–1.74), located near HLA-DRB1. Inclusion of data from the first GWAS (combined N = 2289) identified 47 SNPs in the class II HLA region that were significantly associated with podoconiosis (lead SNP also rs9270911 (P = 2.25 × 10−12). No new loci outside of the HLA class II region were identified in this more highly-powered second GWAS. Our findings confirm the HLA class II association with podoconiosis suggesting HLA-mediated abnormal induction and regulation of immune responses may have a direct role in its pathogenesis.
High β-lactam resistance in Gram-negative bacteria associated with kennel cough and cat flu in Egypt
Authors: Khalifa Hazim O. , Oreiby Atef F. , Okanda Takashi , Kato Yasuyuki , Matsumoto Tetsuya
Published: February 2021

Antimicrobial resistance within pets has gained worldwide attention due to pets close contact with humans. This report examined at the molecular level, the antimicrobial resistance mechanisms associated with kennel cough and cat flu. 1378 pets in total were assessed for signs of respiratory infection, and nasal and conjunctival swabs were collected across 76 diseased animals. Phenotypically, 27% of the isolates were characterized by multidrug resistance and possessed high levels of resistance rates to β-lactams. Phenotypic ESBLs/AmpCs production were identified within 40.5% and 24.3% of the isolates, respectively. Genotypically, ESBL- and AmpC-encoding genes were detected in 33.8% and 10.8% of the isolates, respectively, with blaSHV comprising the most identified ESBL, and blaCMY and blaACT present as the AmpC with the highest levels. qnr genes were identified in 64.9% of the isolates, with qnrS being the most prevalent (44.6%). Several antimicrobial resistance determinants were detected for the first time within pets from Africa, including blaCTX-M-37, blaCTX-M-156, blaSHV-11, blaACT-23, blaACT25/31, blaDHA-1, and blaCMY-169. Our results revealed that pets displaying symptoms of respiratory illness are potential sources for pathogenic microbes possessing unique resistance mechanisms which could be disseminated to humans, thus leading to the development of severe untreatable infections in these hosts.
Bioconvection flow in accelerated couple stress nanoparticles with activation energy: bio-fuel applications
Authors: Khan Sami Ullah , Al-Khaled Kamel , Aldabesh A. , Awais Muhammad , Tlili Iskander
Published: February 2021

On the account of significance of bioconvection in biotechnology and several biological systems, valuable contributions have been performed by scientists in current decade. In current framework, a theoretical bioconvection model is constituted to examine the analyzed the thermally developed magnetized couple stress nanoparticles flow by involving narrative flow characteristics namely activation energy, chemical reaction and radiation features. The accelerated flow is organized on the periodically porous stretched configuration. The heat performances are evaluated via famous Buongiorno’s model which successfully reflects the important features of thermophoretic and Brownian motion. The composed fluid model is based on the governing equations of momentum, energy, nanoparticles concentration and motile microorganisms. The dimensionless problem has been solved analytically via homotopic procedure where the convergence of results is carefully examined. The interesting graphical description for the distribution of velocity, heat transfer of nanoparticles, concentration pattern and gyrotactic microorganism significance are presented with relevant physical significance. The variation in wall shear stress is also graphically underlined which shows an interesting periodic oscillation near the flow domain. The numerical interpretation for examining the heat mass and motile density transfer rate is presented in tubular form.
BAX and SMAC regulate bistable properties of the apoptotic caspase system
Authors: McKenna Stephanie , García-Gutiérrez Lucía , Matallanas David , Fey Dirk
Published: February 2021

The initiation of apoptosis is a core mechanism in cellular biology by which organisms control the removal of damaged or unnecessary cells. The irreversible activation of caspases is essential for apoptosis, and mathematical models have demonstrated that the process is tightly regulated by positive feedback and a bistable switch. BAX and SMAC are often dysregulated in diseases such as cancer or neurodegeneration and are two key regulators that interact with the caspase system generating the apoptotic switch. Here we present a mathematical model of how BAX and SMAC control the apoptotic switch. Formulated as a system of ordinary differential equations, the model summarises experimental and computational evidence from the literature and incorporates the biochemical mechanisms of how BAX and SMAC interact with the components of the caspase system. Using simulations and bifurcation analysis, we find that both BAX and SMAC regulate the time-delay and activation threshold of the apoptotic switch. Interestingly, the model predicted that BAX (not SMAC) controls the amplitude of the apoptotic switch. Cell culture experiments using siRNA mediated BAX and SMAC knockdowns validated this model prediction. We further validated the model using data of the NCI-60 cell line panel using BAX protein expression as a cell-line specific parameter and show that model simulations correlated with the cellular response to DNA damaging drugs and established a defined threshold for caspase activation that could distinguish between sensitive and resistant melanoma cells. In summary, we present an experimentally validated dynamic model that summarises our current knowledge of how BAX and SMAC regulate the bistable properties of irreversible caspase activation during apoptosis.
Neuropeptide Y (NPY) intranasal delivery alleviates Machado–Joseph disease
Authors: Duarte-Neves Joana , Cavadas Cláudia , Pereira de Almeida Luís
Published: February 2021

Machado–Joseph disease (MJD) is the most common dominantly-inherited ataxia worldwide with no effective treatment to prevent, stop or alleviate its progression. Neuropeptide Y (NPY) is a neuroprotective agent widely expressed in the mammalian brain. Our previous work showed that NPY overexpression mediated by stereotaxically-injected viral vectors mitigates motor deficits and neuropathology in MJD mouse models. To pursue a less invasive translational approach, we investigated whether intranasal administration of NPY would alleviate cerebellar neuropathology and motor and balance impairments in a severe MJD transgenic mouse model. For that, a NPY solution was administered into mice nostrils 5 days a week. Upon 8 weeks of treatment, we observed a mitigation of motor and balance impairments through the analysis of mice behavioral tests (rotarod, beam walking, pole and swimming tests). This was in line with a reduction of cerebellar pathology, evidenced by a preservation of cerebellar granular layer and of Purkinje cells and reduction of mutant ataxin-3 aggregate numbers. Furthermore, intranasal administration of NPY did not alter body weight gain, food intake, amount of body fat nor cholesterol or triglycerides levels. Our findings support the translational potential of intranasal infusion of NPY as a pharmacological intervention in MJD.
High probability of yield gain through conservation agriculture in dry regions for major staple crops
Authors: Su Yang , Gabrielle Benoit , Beillouin Damien , Makowski David
Published: February 2021

Conservation agriculture (CA) has been promoted to mitigate climate change, reduce soil erosion, and provide a variety of ecosystem services. Yet, its impacts on crop yields remains controversial. To gain further insight, we mapped the probability of yield gain when switching from conventional tillage systems (CT) to CA worldwide. Relative yield changes were estimated with machine learning algorithms trained by 4403 paired yield observations on 8 crop species extracted from 413 publications. CA has better productive performance than no-till system (NT), and it stands a more than 50% chance to outperform CT in dryer regions of the world, especially with proper agricultural management practices. Residue retention has the largest positive impact on CA productivity comparing to other management practices. The variations in the productivity of CA and NT across geographical and climatical regions were illustrated on global maps. CA appears as a sustainable agricultural practice if targeted at specific climatic regions and crop species.
Pentapartite fractionation of particles in oral fluids by differential centrifugation
Authors: Hiraga Chiho , Yamamoto Satoshi , Hashimoto Sadamitsu , Kasahara Masataka , Minamisawa Tamiko , Matsumura Sachiko , Katakura Akira , Yajima Yasutomo , Nomura Takeshi , Shiba Kiyotaka
Published: February 2021

Oral fluids (OFs) contain small extracellular vesicles (sEVs or exosomes) that carry disease-associated diagnostic molecules. However, cells generate extracellular vesicles (EVs) other than sEVs, so the EV population is quite heterogeneous. Furthermore, molecules not packaged in EVs can also serve as diagnostic markers. For these reasons, developing a complete picture of particulate matter in the oral cavity is important before focusing on specific subtypes of EVs. Here, we used differential centrifugation to fractionate human OFs from healthy volunteers and patients with oral squamous cell carcinoma into 5 fractions, and we characterized the particles, nucleic acids, and proteins in each fraction. Canonical exosome markers, including CD63, CD9, CD133, and HSP70, were found in all fractions, whereas CD81 and AQP5 were enriched in the 160K fraction, with non-negligible amounts in the 2K fraction. The 2K fraction also contained its characteristic markers that included short derivatives of EGFR and E-cadherin, as well as an autophagosome marker, LC3, and large multi-layered vesicles were observed by electronic microscopy. Most of the DNA and RNA was recovered from the 0.3K and 2K fractions, with some in the 160K fraction. These results can provide guideline information for development of purpose-designed OF-based diagnostic systems.
The design of X-band EPR cavity with narrow detection aperture for in vivo fingernail dosimetry after accidental exposure to ionizing radiation
Authors: Guo Junwang , Luan Xiaoxiao , Tian Ye , Ma Lei , Bi Xiaoguang , Zou Jierui , Dong Guofu , Liu Ye , Li Yonggang , Ning Jing , Wu Ke
Published: February 2021

For the purpose of assessing the radiation dose of the victims involved in the nuclear emergency or radiation accident, a new type of X-band EPR resonant cavity for in vivo fingernail EPR dosimetry was designed and a homemade EPR spectrometer for in vivo fingernail detection was constructed. The microwave resonant mode of the cavity was rectangular TE101, and there was a narrow aperture for fingernail detection opened on the cavity’s wall at the position of high detection sensitivity. The DPPH dot sample and the fingernail samples were measured based on the in vivo fingernail EPR spectrometer. The measurements of the DPPH dot sample verified the preliminary functional applicable of the EPR spectrometer and illustrated the microwave power and modulation response features. The fingernails after irradiation by gamma-ray were measured and the radiation-induced signal was acquired. The results indicated that the cavity and the in vivo EPR dosimeter instrument was able to detect the radiation-induced signal in irradiated fingernail, and preliminarily verified the basic function of the instrument and its potential for emergency dose estimate after a radiation accident.
Correlation of cardiac function and cerebral perfusion in a murine model of subarachnoid hemorrhage
Authors: Neulen Axel , Molitor Michael , Kosterhon Michael , Pantel Tobias , Holzbach Elisa , Rudi Wolf-Stephan , Karbach Susanne H. , Wenzel Philip , Ringel Florian , Thal Serge C.
Published: February 2021

Cerebral hypoperfusion is a key factor for determining the outcome after subarachnoid hemorrhage (SAH). A subset of SAH patients develop neurogenic stress cardiomyopathy (NSC), but it is unclear to what extent cerebral hypoperfusion is influenced by cardiac dysfunction after SAH. The aims of this study were to examine the association between cardiac function and cerebral perfusion in a murine model of SAH and to identify electrocardiographic and echocardiographic signs indicative of NSC. We quantified cortical perfusion by laser SPECKLE contrast imaging, and myocardial function by serial high-frequency ultrasound imaging, for up to 7 days after experimental SAH induction in mice by endovascular filament perforation. Cortical perfusion decreased significantly whereas cardiac output and left ventricular ejection fraction increased significantly shortly post-SAH. Transient pathological ECG and echocardiographic abnormalities, indicating NSC (right bundle branch block, reduced left ventricular contractility), were observed up to 3 h post-SAH in a subset of model animals. Cerebral perfusion improved over time after SAH and correlated significantly with left ventricular end-diastolic volume at 3, 24, and 72 h. The murine SAH model is appropriate to experimentally investigate NSC. We conclude that in addition to cerebrovascular dysfunction, cardiac dysfunction may significantly influence cerebral perfusion, with LVEDV presenting a potential parameter for risk stratification.
3D phonon microscopy with sub-micron axial-resolution
Authors: Smith Richard J. , Pérez-Cota Fernando , Marques Leonel , Clark Matt
Published: February 2021

Brillouin light scattering (BLS) is an emerging method for cell imaging and characterisation. It allows elasticity-related contrast, optical resolution and label-free operation. Phonon microscopy detects BLS from laser generated coherent phonon fields to offer an attractive route for imaging since, at GHz frequencies, the phonon wavelength is sub-optical. Using phonon fields to image single cells is challenging as the signal to noise ratio and acquisition time are often poor. However, recent advances in the instrumentation have enabled imaging of fixed and living cells. This work presents the first experimental characterisation of phonon-based axial resolution provided by the response to a sharp edge. The obtained axial resolution is up to 10 times higher than that of the optical system used to take the measurements. Validation of the results are obtained with various polymer objects, which are in good agreement with those obtained using atomic force microscopy. Edge localisation, and hence profilometry, of a phantom boundary is measured with accuracy and precision of approximately 60 nm and 100 nm respectively. Finally, 3D imaging of fixed cells in culture medium is demonstrated.
The distribution of antibiotic resistance genes in chicken gut microbiota commensals
Authors: Juricova Helena , Matiasovicova Jitka , Kubasova Tereza , Cejkova Darina , Rychlik Ivan
Published: February 2021

Antibiotic resistance in bacterial pathogens or several indicator bacteria is commonly studied but the extent of antibiotic resistance in bacterial commensals colonising the intestinal tract is essentially unknown. In this study, we aimed to investigate the presence of horizontally acquired antibiotic resistance genes among chicken gut microbiota members in 259 isolates with known whole genomic sequences. Altogether 124 isolates contained at least one gene coding for antibiotic resistance. Genes coding for the resistance to tetracyclines (detected in 101 isolates), macrolide-lincosamide-streptogramin B antibiotics (28 isolates) and aminoglycosides (25 isolates) were the most common. The most frequent tetracycline resistance genes were tet(W), tet(32), tet(O) and tet(Q). Lachnospiraceae and Ruminococcaceae frequently encoded tet(W). Lachnospiraceae commonly coded also for tet(32) and tet(O). The tet(44) gene was associated with Erysipelotrichaceae and tet(Q) was detected in the genomes of Bacteroidaceae and Porphyromonadaceae. Without any bias we have shown that antibiotic resistance is quite common in gut commensals. However, a comparison of codon usage showed that the above-mentioned families represent the most common current reservoirs but probably not the original host of the detected resistances.
Methodological synthesis of Bayesian phylodynamics, HIV-TRACE, and GEE: HIV-1 transmission epidemiology in a racially/ethnically diverse Southern U.S. context
Authors: Fujimoto Kayo , Bahl Justin , Wertheim Joel O. , Del Vecchio Natascha , Hicks Joseph T. , Damodaran Lambodhar , Hallmark Camden J. , Lavingia Richa , Mora Ricardo , Carr Michelle , Yang Biru , Schneider John A. , Hwang Lu-Yu , McNeese Marlene
Published: February 2021

This study introduces an innovative methodological approach to identify potential drivers of structuring HIV-1 transmission clustering patterns between different subpopulations in the culturally and racially/ethnically diverse context of Houston, TX, the largest city in the Southern United States. Using 6332 HIV-1 pol sequences from persons newly diagnosed with HIV during the period 2010–2018, we reconstructed HIV-1 transmission clusters, using the HIV-TRAnsmission Cluster Engine (HIV-TRACE); inferred demographic and risk parameters on HIV-1 transmission dynamics by jointly estimating viral transmission rates across racial/ethnic, age, and transmission risk groups; and modeled the degree of network connectivity by using generalized estimating equations (GEE). Our results indicate that Hispanics/Latinos are most vulnerable to the structure of transmission clusters and serve as a bridge population, acting as recipients of transmissions from Whites (3.0 state changes/year) and from Blacks (2.6 state changes/year) as well as sources of transmissions to Whites (1.8 state changes/year) and to Blacks (1.2 state changes/year). There were high rates of transmission and high network connectivity between younger and older Hispanics/Latinos as well as between younger and older Blacks. Prevention and intervention efforts are needed for transmission clusters that involve younger racial/ethnic minorities, in particular Hispanic/Latino youth, to reduce onward transmission of HIV in Houston.
The effect of particle shape on discharge and clogging
Authors: Hafez Ahmed , Liu Qi , Finkbeiner Thomas , Alouhali Raed A. , Moellendick Timothy E. , Santamarina J. Carlos
Published: February 2021

Granular flow is common across different fields from energy resource recovery and mineral processing to grain transport and traffic flow. Migrating particles may jam and form arches that span constrictions and hinder particle flow. Most studies have investigated the migration and clogging of spherical particles, however, natural particles are rarely spherical, but exhibit eccentricity, angularity and roughness. New experiments explore the discharge of cubes, 2D crosses, 3D crosses and spheres under dry conditions and during particle-laden fluid flow. Variables include orifice-to-particle size ratio and solidity. Cubes and 3D crosses are the most prone to clogging because of their ability to interlock or the development of face-to-face contacts that can resist torque and enhance bridging. Spheres arriving to the orifice must be correctly positioned to create stable bridges, while flat 2D crosses orient their longest axes in the direction of flowlines across the orifice and favor flow. Intermittent clogging causes kinetic retardation in particle-laden flow even in the absence of inertial effects; the gradual increase in the local particle solidity above the constriction enhances particle interactions and the probability of clogging. The discharge volume before clogging is a Poisson process for small orifice-to-particle size ratio; however, the clogging probability becomes history-dependent for non-spherical particles at large orifice-to-particle size ratio and high solidities, i.e., when particle–particle interactions and interlocking gain significance.
A CRISPR-Cas9 based shuffle system for endogenous histone H3 and H4 combinatorial mutagenesis
Authors: Fu Yu , Zhu Zhenglin , Meng Geng , Zhang Rijun , Zhang Yueping
Published: February 2021

Post-translational modifications of histone proteins greatly impact gene expression and cell fate decisions in eukaryotes. To study these, it is important to develop a convenient, multiplex, and efficient method to precisely introduce mutations to histones. Because eukaryotic cells usually contain multiple copies of histone genes, it is a challenge to mutate all histones at the same time by the traditional homologous recombination method. Here, we developed a CRISPR-Cas9 based shuffle system in Saccharomyces cerevisiae, to generate point mutations on both endogenous histone H3 and H4 genes in a rapid, seamless and multiplex fashion. Using this method, we generated yeast strains containing histone triple H3–K4R–K36R–K79R mutants and histone combinatorial H3–K56Q–H4–K59A double mutants with high efficiencies (70–80%). This CRISPR-Cas9 based mutagenesis system could be an invaluable tool to the epigenetics field.
Automated quantification of posterior vitreous inflammation: optical coherence tomography scan number requirements
Authors: Terheyden Jan Henrik , Ometto Giovanni , Montesano Giovanni , Wintergerst Maximilian W. M. , Langner Magdalena , Liu Xiaoxuan , Keane Pearse A. , Crabb David P. , Denniston Alastair K. , Finger Robert P.
Published: February 2021

Quantifying intraocular inflammation is crucial in managing uveitis patients. We assessed the minimum B-scan density for reliable automated vitreous intensity (VI) assessment, using a novel approach based on optical coherence tomography (OCT). OCT volume scans centered on the macula were retrospectively collected in patients with uveitis. Nine B-scans per volume scan at fixed locations were automatically analyzed. The following B-scan selections were compared against the average score of 9 B-scans per volume scan as a reference standard: 1/3/5/7 central scans (1c/3c/5c/7c), 3 widely distributed scans (3w). Image data of 49 patients (31 females) were included. The median VI was 0.029 (IQR: 0.032). The intra-class-correlation coefficient of the VI across the 9 B-scans was 0.923. The median difference from the reference standard ranged between 0.001 (7c) and 0.006 (1c). It was significantly lower for scan selection 3w than 5c, p(adjusted) = 0.022, and lower for selection 7c than 3w, p(adjusted) = 0.003. The scan selections 7c and 3w showed the two highest areas under the receiver operating curve (0.985 and 0.965, respectively). Three widely distributed B-scans are sufficient to quantify VI reliably. Highest reliability was achieved using 7 central B-scans. Automated quantification of VI in uveitis is reliable and requires only few OCT B-scans.
Development and first biomechanical validation of a score to predict bone implant interface stability based on clinical qCT scans
Authors: Wähnert Dirk , Frank Andre , Ueberberg Johanna , Heilmann Lukas F. , Sauzet Odile , Raschke Michael J. , Gehweiler Dominic
Published: February 2021

Sufficient implant anchoring in osteoporotic bone is one major challenge in trauma and orthopedic surgery. In these cases, preoperative planning of osteosynthesis is becoming increasingly important. This study presents the development and first biomechanical validation of a bone-implant-anchorage score based on clinical routine quantitative computer tomography (qCT) scans. 10 pairs of fresh frozen femora (mean age 77.4 years) underwent clinical qCT scans after placing 3 referential screws (for matching with the second scan). Afterwards, three 4.5 mm cortical screws (DePuy Synthes, Zuchwil, Switzerland) were placed in each distal femur in the dia-metaphyseal transition followed by the second CT scan. The femur was segmented using thresholding and its outer shape was visualized as a surface model. A 3D model of the cortex screw in STL format was used to model the screw surface precisely. For each femur, the 3 cortex screw models were exactly positioned at the locations previously determined using the second CT scan. The BMD value was calculated at the center of each triangle as an interpolation from the measured values at the three vertices (triangle corners) in the CT. Scores are based on the sum of all the triangles’ areas multiplied by their BMD values. Four different scores were calculated. A screw pull-out test was performed until loss of resistance. A quadratic model adequately describes the relation between all the scores and pull-out values. The square of the best score explains just fewer than 70% of the total variance of the pull-out values and the standardized residual which were approximately normally distributed. In addition, there was a significant correlation between this score and the peak pull-out force (p < 0.001). The coefficient of determination was 0.82. The presented score has the potential to improve preoperative planning by adding the mechanical to the anatomical dimension when planning screw placement.
Assessment of common housekeeping genes as reference for gene expression studies using RT-qPCR in mouse choroid plexus
Authors: Ho Kim Hoa , Patrizi Annarita
Published: February 2021

Choroid plexus (ChP), a vascularized secretory epithelium located in all brain ventricles, plays critical roles in development, homeostasis and brain repair. Reverse transcription quantitative real-time PCR (RT-qPCR) is a popular and useful technique for measuring gene expression changes and also widely used in ChP studies. However, the reliability of RT-qPCR data is strongly dependent on the choice of reference genes, which are supposed to be stable across all samples. In this study, we validated the expression of 12 well established housekeeping genes in ChP in 2 independent experimental paradigms by using popular stability testing algorithms: BestKeeper, DeltaCq, geNorm and NormFinder. Rer1 and Rpl13a were identified as the most stable genes throughout mouse ChP development, while Hprt1 and Rpl27 were the most stable genes across conditions in a mouse sensory deprivation experiment. In addition, Rpl13a, Rpl27 and Tbp were mutually among the top five most stable genes in both experiments. Normalisation of Ttr and Otx2 expression levels using different housekeeping gene combinations demonstrated the profound effect of reference gene choice on target gene expression. Our study emphasized the importance of validating and selecting stable housekeeping genes under specific experimental conditions.