bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accuracy mechanism of eukaryotic ribosome translocation
Authors: Djumagulov Muminjon , Demeshkina Natalia , Jenner Lasse , Rozov Alexey , Yusupov Marat , Yusupova Gulnara 
Published: December 2021

AbstractTranslation of the genetic code into proteins is realized through repetitions of synchronous translocation of messenger RNA (mRNA) and transfer RNAs (tRNA) through the ribosome. In eukaryotes translocation is ensured by elongation factor 2 (eEF2), which catalyses the process and actively contributes to its accuracy1. Although numerous studies point to critical roles for both the conserved eukaryotic posttranslational modification diphthamide in eEF2 and tRNA modifications in supporting the accuracy of translocation, detailed molecular mechanisms describing their specific functions are poorly understood. Here we report a high-resolution X-ray structure of the eukaryotic 80S ribosome in a translocation-intermediate state containing mRNA, naturally modified eEF2 and tRNAs. The crystal structure reveals a network of stabilization of codon–anticodon interactions involving diphthamide1 and the hypermodified nucleoside wybutosine at position 37 of phenylalanine tRNA, which is also known to enhance translation accuracy2. The model demonstrates how the decoding centre releases a codon–anticodon duplex, allowing its movement on the ribosome, and emphasizes the function of eEF2 as a ‘pawl’ defining the directionality of translocation3. This model suggests how eukaryote-specific elements of the 80S ribosome, eEF2 and tRNAs undergo large-scale molecular reorganizations to ensure maintenance of the mRNA reading frame during the complex process of translocation.
A point-mutation in the C-domain of CMP-sialic acid synthetase leads to lethality of medaka due to protein insolubility
Authors: Wu Di , Arakawa Hiromu , Fujita Akiko , Hashimoto Hisashi , Hibi Masahiko , Naruse Kiyoshi , Kamei Yasuhiro , Sato Chihiro , Kitajima Ken 
Published: December 2021

AbstractVertebrate CMP-sialic acid synthetase (CSS), which catalyzes the synthesis of CMP-sialic acid (CMP-Sia), consists of a 28 kDa-N-domain and a 20 kDa-C-domain. The N-domain is known to be a catalytic domain; however, the significance of the C-domain still remains unknown. To elucidate the function of the C-domain at the organism level, we screened the medaka TILLING library and obtained medaka with non-synonymous mutations (t911a), or single amino acid substitutions of CSS, L304Q, in the C-domain. Prominently, most L304Q medaka was lethal within 19 days post-fertilization (dpf). L304Q young fry displayed free Sia accumulation, and impairment of sialylation, up to 8 dpf. At 8 dpf, a marked abnormality in ventricular contraction and skeletal myogenesis was observed. To gain insight into the mechanism of L304Q-induced abnormalities, L304Q was biochemically characterized. Although bacterially expressed soluble L304Q and WT showed the similar Vmax/Km values, very few soluble L304Q was detected when expressed in CHO cells in sharp contrast to the WT. Additionally, the thermostability of various mutations of L304 greatly decreased, except for WT and L304I. These results suggest that L304 is important for the stability of CSS, and that an appropriate level of expression of soluble CSS is significant for animal survival.
A wearable microwave instrument can detect and monitor traumatic abdominal injuries in a porcine model
Authors: Candefjord Stefan , Nguyen Linh , Buendia Ruben , Oropeza-Moe Marianne , Andersen Nina Gjerde , Fhager Andreas , Persson Mikael , Elam Mikael , Oveland Nils Petter 
Published: December 2021

AbstractAbdominal injury is a frequent cause of death for trauma patients, and early recognition is essential to limit fatalities. There is a need for a wearable sensor system for prehospital settings that can detect and monitor bleeding in the abdomen (hemoperitoneum). This study evaluates the potential for microwave technology to fill that gap. A simple prototype of a wearable microwave sensor was constructed using eight antennas. A realistic porcine model of hemoperitoneum was developed using anesthetized pigs. Ten animals were measured at healthy state and at two sizes of bleeding. Statistical tests and a machine learning method were used to evaluate blood detection sensitivity. All subjects presented similar changes due to accumulation of blood, which dampened the microwave signal ($$p < 0.05$$

p
<
0.05

). The machine learning analysis yielded an area under the receiver operating characteristic (ROC) curve (AUC) of 0.93, showing 100% sensitivity at 90% specificity. Large inter-individual variability of the healthy state signal complicated differentiation of bleedings from healthy state. A wearable microwave instrument has potential for accurate detection and monitoring of hemoperitoneum, with automated analysis making the instrument easy-to-use. Future hardware development is necessary to suppress measurement system variability and enable detection of smaller bleedings.
Branching patterns of the afferent branchial arteries and their phylogenetic significance in rays (Batoidea)
Authors: Soares Karla D. A. , Toledo-Piza Mônica 
Published: December 2021

AbstractRays of the superorder Batoidea comprise the most diverse group of chondrichthyans in terms of valid species and morphological disparity. Up to the present little agreement is observed in studies based on morphological and molecular data focused on uncovering the interrelationships within Batoidea. Morphology-based phylogenies of batoids have not included characters related to the afferent branchial arteries, and little is known about the variation in this anatomical complex in rays. Herein, representatives of 32 genera from 19 families currently recognized of rays were examined as well as some shark taxa. Seven new characters are proposed and tested in two different analyses, one on their own and in the other they were added to the morphological data matrix of the most recent analysis of interrelationships within Batoidea. The arrangement of afferent branchial arteries differs mainly among orders and families of batoids. The absence of a common trunk from which the three posteriormost afferent arteries branch is interpreted as a synapomorphy for Myliobatiformes and the presence of a coronary cranial artery as an autapomorphy for Mobula hypostoma. A close spatial relationship between the second and third afferent arteries within the common branch from the ventral aorta is proposed as a synapomorphy for Rajiformes with a secondary modification in Sympterygia. Data about patterns in afferent branchial arteries in additional taxa such as Squaliformes and Chimaeriformes are needed to better understand the evolution of this character complex among chondrichthyans.
A message of the majority with scientific evidence encourages young people to show their prosocial nature in COVID-19 vaccination
Authors: Tanaka Toshiko , Nihonsugi Tsuyoshi , Ohtake Fumio , Haruno Masahiko 
Published: December 2021

AbstractThe most promising way to prevent the explosive spread of COVID-19 infection is to achieve herd immunity through vaccination. It is therefore important to motivate those who are less willing to be vaccinated. To address this issue, we conducted an online survey of 6232 Japanese people to investigate age- and gender-dependent differences in attitudes towards COVID-19 vaccination and the underlying psychological processes. We asked participants to read one of nine different messages about COVID-19 vaccination and rate their willingness to be vaccinated. We also collected their 17 social personality trait scores and demographic information. We found that males 10–20 years old were least willing to be vaccinated. We also found that prosocial traits are the driving force for young people, but the motivation in older people also depends on risk aversion and self-interest. Furthermore, an analysis of 9 different messages demonstrated that for young people (particularly males), the message emphasizing the majority’s intention to vaccinate and scientific evidence for the safety of the vaccination had the strongest positive effect on the willingness to be vaccinated, suggesting that the “majority + scientific evidence” message nudges young people to show their prosocial nature in action.
Vesicular and extravesicular protein analyses from the airspaces of ozone-exposed mice revealed signatures associated with mucoinflammatory lung disease
Authors: Choudhary Ishita , Vo Thao , Paudel Kshitiz , Wen Xue , Gupta Richa , Kesimer Mehmet , Patial Sonika , Saini Yogesh 
Published: December 2021

AbstractLung epithelial lining fluid (ELF) harbors a variety of proteins that influence homeostatic and stress responses in the airspaces. Exosomes, nano-sized extracellular vesicles, contain many proteins that vary in abundance and composition based on the prevailing conditions. Ozone causes inflammatory responses in the airspaces of experimental animals and humans. However, the exosomal protein signatures contained within the ELF from ozone-exposed lung airspaces remain poorly characterized. To explore this, we hypothesized that ozone triggers the release of exosome-bound inflammatory proteins from various cells that reflect mucoobstructive lung disease. Accordingly, we repetitively exposed adult male and female C57BL/6 mice to HEPA-filtered air (air) or 0.8 ppm ozone (4 h per day) for 14 days (five consecutive days of exposure, 2 days of rest, five consecutive days of exposure, 2 days of rest, four consecutive days of exposure). Exosome-bound proteomic signatures, as well as the levels of soluble inflammatory mediators in the bronchoalveolar lavage fluid (BALF), were determined 12–16 h after the last exposure. Principal component analyses of the exosome-bound proteome revealed a clear distinction between air-exposed and ozone-exposed mice, as well as between ozone-exposed males and ozone-exposed females. In addition to 575 proteins that were enriched in both sexes upon ozone exposure, 243 and 326 proteins were enriched uniquely in ozone-exposed males and females, respectively. Ingenuity pathway analyses on enriched proteins between ozone- and air-exposed mice revealed enrichment of pro-inflammatory pathways. More specifically, macrophage activation-related proteins were enriched in exosomes from ozone-exposed mice. Cytokine analyses on the BALF revealed elevated levels of G-CSF, KC, IP-10, IL-6, and IL-5 in ozone-exposed mice. Finally, the histopathological assessment revealed significantly enhanced intracellular localization of mucoinflammatory proteins including MUC5B and FIZZ1 in ozone-exposed mice in a cell-specific manner indicating the cellular sources of the proteins that are ferried in the exosomes upon ozone-induced lung injury. Collectively, this study identified exosomal, secretory, and cell-specific proteins and biological pathways following repetitive exposure of mice to ozone.
Counting using deep learning regression gives value to ecological surveys
Authors: Hoekendijk Jeroen P. A. , Kellenberger Benjamin , Aarts Geert , Brasseur Sophie , Poiesz Suzanne S. H. , Tuia Devis 
Published: December 2021

AbstractMany ecological studies rely on count data and involve manual counting of objects of interest, which is time-consuming and especially disadvantageous when time in the field or lab is limited. However, an increasing number of works uses digital imagery, which opens opportunities to automatise counting tasks. In this study, we use machine learning to automate counting objects of interest without the need to label individual objects. By leveraging already existing image-level annotations, this approach can also give value to historical data that were collected and annotated over longer time series (typical for many ecological studies), without the aim of deep learning applications. We demonstrate deep learning regression on two fundamentally different counting tasks: (i) daily growth rings from microscopic images of fish otolith (i.e., hearing stone) and (ii) hauled out seals from highly variable aerial imagery. In the otolith images, our deep learning-based regressor yields anRMSEof 3.40 day-rings and an$$R^2$$R2of 0.92. Initial performance in the seal images is lower (RMSEof 23.46 seals and$$R^2$$R2of 0.72), which can be attributed to a lack of images with a high number of seals in the initial training set, compared to the test set. We then show how to improve performance substantially (RMSEof 19.03 seals and$$R^2$$R2of 0.77) by carefully selecting and relabelling just 100 additional training images based on initial model prediction discrepancy. The regression-based approach used here returns accurate counts ($$R^2$$R2of 0.92 and 0.77 for the rings and seals, respectively), directly usable in ecological research.
Persistent pulmonary pathology after COVID-19 is associated with high viral load, weak antibody response, and high levels of matrix metalloproteinase-9
Authors: Lerum Tøri Vigeland , Maltzahn Niklas Nyboe , Aukrust Pål , Trøseid Marius , Henriksen Katerina Nezvalova , Kåsine Trine , Dyrhol-Riise Anne-Ma , Stiksrud Birgitte , Haugli Mette , Blomberg Bjørn , Kittang Bård Reiakvam , Johannessen Asgeir , Hannula Raisa , Aballi Saad , Kildal Anders Benjamin , Eiken Ragnhild , Dahl Tuva Børresdatter , Lund-Johansen Fridtjof , Müller Fredrik , Rodriguez Jezabel Rivero , Meltzer Carin , Einvik Gunnar , Ueland Thor , Olsen Inge Christoffer ,   NOR-SOLIDARITY Consortium, Pettersen Frank Olav , Holten Aleksander Rygh , Tonby Kristian , Reikvam Dag Henrik , Røstad Kjerstin , Jenum Synne , Hesstvedt Liv , Vaage Eline Brenno , Kolderup Anette , Tran Trung , Andersen Jan Terje , Holberg-Petersen Mona , Johal Simreen Kaur , Berg Åse , Tveita Anders , Ernst Gernot , Heggelund Lars , Thoresen Lars , Müller Karl Erik , Hoff Dag Arne Lihaug , Olsen Roy Bjørkholt , Finbråten Ane-Krisitne , Hoel Hedda , Mathiessen Alexander , Vinge Leif Erik , Nordberg Lena Bugge , Manotheepan Ravinea , Stenvik Grethe-Elisabeth , Rasmussen Hans Schmidt , Thorkildsen Ruth Foseide , Mielnik Pawel , Le Lan Ai Kieu , Ystrøm Carl Magnus , Molvik Richard Alexander , Skei Nina Vibeche , Dalgard Olav , Åsheim-Hansen Bjørn , Halstensen Anne Marie , Brynhildsen Jorunn , Ghanima Waleed , Skogen Vegard , Mohn Krisine Greve Isdahl , Kvåle Reidar , Langeland Nina , Gustad Lise Tuset , Saxhaug Lars Mølgaard , Fladeby Cathrine , Dudman Susanne , Steffensen Anne , Barratt-Due Andreas , Aaløkken Trond Mogens , Skjønsberg Ole Henning 
Published: December 2021

AbstractThe association between pulmonary sequelae and markers of disease severity, as well as pro-fibrotic mediators, were studied in 108 patients 3 months after hospital admission for COVID-19. The COPD assessment test (CAT-score), spirometry, diffusion capacity of the lungs (DLCO), and chest-CT were performed at 23 Norwegian hospitals included in the NOR-SOLIDARITY trial, an open-labelled, randomised clinical trial, investigating the efficacy of remdesivir and hydroxychloroquine (HCQ). Thirty-eight percent had a CAT-score ≥ 10. DLCO was below the lower limit of normal in 29.6%. Ground-glass opacities were present in 39.8% on chest-CT, parenchymal bands were found in 41.7%. At admission, low pO2/FiO2 ratio, ICU treatment, high viral load, and low antibody levels, were predictors of a poorer pulmonary outcome after 3 months. High levels of matrix metalloproteinase (MMP)-9 during hospitalisation and at 3 months were associated with persistent CT-findings. Except for a negative effect of remdesivir on CAT-score, we found no effect of remdesivir or HCQ on long-term pulmonary outcomes. Three months after hospital admission for COVID-19, a high prevalence of respiratory symptoms, reduced DLCO, and persistent CT-findings was observed. Low pO2/FiO2 ratio, ICU-admission, high viral load, low antibody levels, and high levels of MMP-9 were associated with a worse pulmonary outcome.
Metabolite and thymocyte development defects in ADA-SCID mice receiving enzyme replacement therapy
Authors: Moretti Federico A. , Giardino Giuliana , Attenborough Teresa C. H. , Gkazi Athina Soragia , Margetts Ben K. , la Marca Giancarlo , Fairbanks Lynette , Crompton Tessa , Gaspar H. Bobby 
Published: December 2021

AbstractDeficiency of adenosine deaminase (ADA, EC3.5.4.4), a housekeeping enzyme intrinsic to the purine salvage pathway, leads to severe combined immunodeficiency (SCID) both in humans and mice. Lack of ADA results in the intracellular accumulation of toxic metabolites which have effects on T cell development and function. While untreated ADA-SCID is a fatal disorder, there are different therapeutic options available to restore ADA activity and reconstitute a functioning immune system, including enzyme replacement therapy (ERT). Administration of ERT in the form of pegylated bovine ADA (PEG-ADA) has proved a life-saving though non-curative treatment for ADA-SCID patients. However, in many patients treated with PEG-ADA, there is suboptimal immune recovery with low T and B cell numbers. Here, we show reduced thymus cellularity in ADA-SCID mice despite weekly PEG-ADA treatment. This was associated with lack of effective adenosine (Ado) detoxification in the thymus. We also show that thymocyte development in ADA-deficient thymi is arrested at the DN3-to-DN4 stage transition with thymocytes undergoing dATP-induced apoptosis rather than defective TCRβ rearrangement or β-selection. Our studies demonstrate at a detailed level that exogenous once-a-week enzyme replacement does not fully correct intra-thymic metabolic or immunological abnormalities associated with ADA deficiency.
Portable on-chip colorimetric biosensing platform integrated with a smartphone for label/PCR-free detection of Cryptosporidium RNA
Authors: Luka George S. , Nowak Ephraim , Toyata Quin Robert , Tasnim Nishat , Najjaran Homayoun , Hoorfar Mina 
Published: December 2021

AbstractCryptosporidium, a protozoan pathogen, is a leading threat to public health and the economy. Herein, we report the development of a portable, colorimetric biosensing platform for the sensitive, selective and label/PCR-free detection of Cryptosporidium RNA using oligonucleotides modified gold nanoparticles (AuNPs). A pair of specific thiolated oligonucleotides, complementary to adjacent sequences on Cryptosporidium RNA, were attached to AuNPs. The need for expensive laboratory-based equipment was eliminated by performing the colorimetric assay on a micro-fabricated chip in a 3D-printed holder assembly. A smartphone camera was used to capture an image of the color change for quantitative analysis. The detection was based on the aggregation of the gold nanoparticles due to the hybridization between the complementary Cryptosporidium RNA and the oligonucleotides immobilized on the AuNPs surface. In the complementary RNA’s presence, a distinctive color change of the AuNPs (from red to blue) was observed by the naked eye. However, in the presence of non-complementary RNA, no color change was observed. The sensing platform showed wide linear responses between 5 and 100 µM with a low detection limit of 5 µM of Cryptosporidium RNA. Additionally, the sensor developed here can provide information about different Cryptosporidium species present in water resources. This cost-effective, easy-to-use, portable and smartphone integrated on-chip colorimetric biosensor has great potential to be used for real-time and portable POC pathogen monitoring and molecular diagnostics.
A clinical, aetiological, and public health perspective on central nervous system infections in Bolivia, 2017–2018
Authors: Saba Villarroel Paola Mariela , Castro Soto María del Rosario , Melendres Flores Oriana , Peralta Landívar Alejandro , Calderón María E. , Loayza Roxana , Boucraut José , Thirion Laurence , Dubot-Pérès Audrey , Ninove Laetitia , de Lamballerie Xavier 
Published: December 2021

AbstractCentral nervous system (CNS) infections are important causes of morbidity and mortality worldwide. In Bolivia, aetiologies, case fatality, and determinants of outcome are poorly characterised. We attempted to investigate such parameters to guide diagnosis, treatment, prevention, and health policy. From Nov-2017 to Oct-2018, we prospectively enrolled 257 inpatients (20.2% HIV-positive patients) of all ages from healthcare centers of Cochabamba and Santa Cruz, Bolivia with a suspected CNS infection and a lumbar puncture performed. Biological diagnosis included classical microbiology, molecular, serological and immunohistochemical tests. An infectious aetiology was confirmed in 128/257 (49.8%) inpatients, including, notably among confirmed single and co-infections, Cryptococcus spp. (41.7%) and Mycobacterium tuberculosis (27.8%) in HIV-positive patients, and Mycobacterium tuberculosis (26.1%) and Streptococcus pneumoniae (18.5%) in HIV-negative patients. The total mortality rate was high (94/223, 42.1%), including six rabies cases. In multivariate logistic regression analysis, mortality was associated with thrombocytopenia (Odds ratio (OR) 5.40, 95%-CI 2.40–11.83) and hydrocephalus (OR 4.07, 95%-CI 1.35–12.23). The proportion of untreated HIV patients, late presentations of neurotuberculosis, the rate of pneumococcal cases, and rabies patients who did not benefit from a post-exposure prophylaxis, suggest that decreasing the burden of CNS infections requires reinforcing health policy regarding tuberculosis, rabies, S. pneumoniae vaccination, and HIV-infections.
Lightweight mediated semi-quantum key distribution protocol with a dishonest third party based on Bell states
Authors: Tsai Chia-Wei , Yang Chun-Wei 
Published: December 2021

AbstractThe mediated semi-quantum key distribution (MSQKD) protocol is an important research issue that lets two classical participants share secret keys securely between each other with the help of a third party (TP). However, in the existing MSQKD protocols, there are two improvable issues, namely (1) the classical participants must be equipped with expensive detectors to avoid Trojan horse attacks and (2) the trustworthiness level of TP must be honest. To the best of our knowledge, none of the existing MSQKD protocols can resolve both these issues. Therefore, this study takes Bell states as the quantum resource to propose a MSQKD protocol, in which the classical participants do not need a Trojan horse detector and the TP is dishonest. Furthermore, the proposed protocol is shown to be secure against well-known attacks and the classical participants only need two quantum capabilities. Therefore, in comparison to the existing MSQKD protocols, the proposed protocol is better practical.