bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and characterization of a novel enhancer in the HTLV-1 proviral genome
Authors: Matsuo Misaki , Ueno Takaharu , Monde Kazuaki , Sugata Kenji , Tan Benjy Jek Yang , Rahman Akhinur , Miyazato Paola , Uchiyama Kyosuke , Islam Saiful , Katsuya Hiroo , Nakajima Shinsuke , Tokunaga Masahito , Nosaka Kisato , Hata Hiroyuki , Utsunomiya Atae , Fujisawa Jun-ichi , Satou Yorifumi 
Published: May 2022

AbstractHuman T-cell leukemia virus type 1 (HTLV-1) is a retrovirus that causes adult T-cell leukemia/lymphoma (ATL), a cancer of infected CD4+ T-cells. There is both sense and antisense transcription from the integrated provirus. Sense transcription tends to be suppressed, but antisense transcription is constitutively active. Various efforts have been made to elucidate the regulatory mechanism of HTLV-1 provirus for several decades; however, it remains unknown how HTLV-1 antisense transcription is maintained. Here, using proviral DNA-capture sequencing, we found a previously unidentified viral enhancer in the middle of the HTLV-1 provirus. The transcription factors, SRF and ELK-1, play a pivotal role in the activity of this enhancer. Aberrant transcription of genes in the proximity of integration sites was observed in freshly isolated ATL cells. This finding resolves certain long-standing questions concerning HTLV-1 persistence and pathogenesis. We anticipate that the DNA-capture-seq approach can be applied to analyze the regulatory mechanisms of other oncogenic viruses integrated into the host cellular genome.
What sets aeolian dune height?
Authors: Gunn Andrew , Casasanta Giampietro , Di Liberto Luca , Falcini Federico , Lancaster Nicholas , Jerolmack Douglas J. 
Published: May 2022

AbstractWherever a loose bed of sand is subject to sufficiently strong winds, aeolian dunes form at predictable wavelengths and growth rates. As dunes mature and coarsen, however, their growth trajectories become more idiosyncratic; nonlinear effects, sediment supply, wind variability and geologic constraints become increasingly relevant, resulting in complex and history-dependent dune amalgamations. Here we examine a fundamental question: do aeolian dunes stop growing and, if so, what determines their ultimate size? Earth’s major sand seas are populated by giant sand dunes, evolved over tens of thousands of years. We perform a global analysis of the topography of these giant dunes, and their associated atmospheric forcings and geologic constraints, and we perform numerical experiments to gain insight on temporal evolution of dune growth. We find no evidence of a previously proposed limit to dune size by atmospheric boundary layer height. Rather, our findings indicate that dunes may grow indefinitely in principle; but growth depends on morphology, slows with increasing size, and may ultimately be limited by sand supply.
Alternative splicing modulation by G-quadruplexes
Authors: Georgakopoulos-Soares Ilias , Parada Guillermo E. , Wong Hei Yuen , Medhi Ragini , Furlan Giulia , Munita Roberto , Miska Eric A. , Kwok Chun Kit , Hemberg Martin 
Published: May 2022

AbstractAlternative splicing is central to metazoan gene regulation, but the regulatory mechanisms are incompletely understood. Here, we show that G-quadruplex (G4) motifs are enriched ~3-fold near splice junctions. The importance of G4s in RNA is emphasised by a higher enrichment for the non-template strand. RNA-seq data from mouse and human neurons reveals an enrichment of G4s at exons that were skipped following depolarisation induced by potassium chloride. We validate the formation of stable RNA G4s for three candidate splice sites by circular dichroism spectroscopy, UV-melting and fluorescence measurements. Moreover, we find that sQTLs are enriched at G4s, and a minigene experiment provides further support for their role in promoting exon inclusion. Analysis of >1,800 high-throughput experiments reveals multiple RNA binding proteins associated with G4s. Finally, exploration of G4 motifs across eleven species shows strong enrichment at splice sites in mammals and birds, suggesting an evolutionary conserved splice regulatory mechanism.
Multivariate genome-wide association study on tissue-sensitive diffusion metrics highlights pathways that shape the human brain
Authors: Fan Chun Chieh , Loughnan Robert , Makowski Carolina , Pecheva Diliana , Chen Chi-Hua , Hagler Donald J. , Thompson Wesley K. , Parker Nadine , van der Meer Dennis , Frei Oleksandr , Andreassen Ole A. , Dale Anders M. 
Published: May 2022

AbstractThe molecular determinants of tissue composition of the human brain remain largely unknown. Recent genome-wide association studies (GWAS) on this topic have had limited success due to methodological constraints. Here, we apply advanced whole-brain analyses on multi-shell diffusion imaging data and multivariate GWAS to two large scale imaging genetic datasets (UK Biobank and the Adolescent Brain Cognitive Development study) to identify and validate genetic association signals. We discover 503 unique genetic loci that have impact on multiple regions of human brain. Among them, more than 79% are validated in either of two large-scale independent imaging datasets. Key molecular pathways involved in axonal growth, astrocyte-mediated neuroinflammation, and synaptogenesis during development are found to significantly impact the measured variations in tissue-specific imaging features. Our results shed new light on the biological determinants of brain tissue composition and their potential overlap with the genetic basis of neuropsychiatric disorders.
A reversible mitochondrial complex I thiol switch mediates hypoxic avoidance behavior in C. elegans
Authors: Onukwufor John O. , Farooqi M. Arsalan , Vodičková Anežka , Koren Shon A. , Baldzizhar Aksana , Berry Brandon J. , Beutner Gisela , Porter George A. , Belousov Vsevolod , Grossfield Alan , Wojtovich Andrew P. 
Published: May 2022

AbstractC. elegans react to metabolic distress caused by mismatches in oxygen and energy status via distinct behavioral responses. At the molecular level, these responses are coordinated by under-characterized, redox-sensitive processes, thought to initiate in mitochondria. Complex I of the electron transport chain is a major site of reactive oxygen species (ROS) production and is canonically associated with oxidative damage following hypoxic exposure. Here, we use a combination of optogenetics and CRISPR/Cas9-mediated genome editing to exert spatiotemporal control over ROS production. We demonstrate a photo-locomotory remodeling of avoidance behavior by local ROS production due to the reversible oxidation of a single thiol on the complex I subunit NDUF-2.1. Reversible thiol oxidation at this site is necessary and sufficient for the behavioral response to hypoxia, does not respond to ROS produced at more distal sites, and protects against lethal hypoxic exposure. Molecular modeling suggests that oxidation at this thiol residue alters the ability for NDUF-2.1 to coordinate electron transfer to coenzyme Q by destabilizing the Q-binding pocket, causing decreased complex I activity. Overall, site-specific ROS production regulates behavioral responses and these findings provide a mechanistic target to suppress the detrimental effects of hypoxia.
Pantothenate kinase 2 interacts with PINK1 to regulate mitochondrial quality control via acetyl-CoA metabolism
Authors: Huang Yunpeng , Wan Zhihui , Tang Yinglu , Xu Junxuan , Laboret Bretton , Nallamothu Sree , Yang Chenyu , Liu Boxiang , Lu Rongze Olivia , Lu Bingwei , Feng Juan , Cao Jing , Hayflick Susan , Wu Zhihao , Zhou Bing 
Published: May 2022

AbstractHuman neurodegenerative disorders often exhibit similar pathologies, suggesting a shared aetiology. Key pathological features of Parkinson’s disease (PD) are also observed in other neurodegenerative diseases. Pantothenate Kinase-Associated Neurodegeneration (PKAN) is caused by mutations in the human PANK2 gene, which catalyzes the initial step of de novo CoA synthesis. Here, we show that fumble (fbl), the human PANK2 homolog in Drosophila, interacts with PINK1 genetically. fbl and PINK1 mutants display similar mitochondrial abnormalities, and overexpression of mitochondrial Fbl rescues PINK1 loss-of-function (LOF) defects. Dietary vitamin B5 derivatives effectively rescue CoA/acetyl-CoA levels and mitochondrial function, reversing the PINK1 deficiency phenotype. Mechanistically, Fbl regulates Ref(2)P (p62/SQSTM1 homolog) by acetylation to promote mitophagy, whereas PINK1 regulates fbl translation by anchoring mRNA molecules to the outer mitochondrial membrane. In conclusion, Fbl (or PANK2) acts downstream of PINK1, regulating CoA/acetyl-CoA metabolism to promote mitophagy, uncovering a potential therapeutic intervention strategy in PD treatment.
The representation of context in mouse hippocampus is preserved despite neural drift
Authors: Keinath Alexandra T. , Mosser Coralie-Anne , Brandon Mark P. 
Published: May 2022

AbstractThe hippocampus is thought to mediate episodic memory through the instantiation and reinstatement of context-specific cognitive maps. However, recent longitudinal experiments have challenged this view, reporting that most hippocampal cells change their tuning properties over days even in the same environment. Often referred to as neural or representational drift, these dynamics raise questions about the capacity and content of the hippocampal code. One such question is whether and how these long-term dynamics impact the hippocampal code for context. To address this, we image large CA1 populations over more than a month of daily experience as freely behaving mice participate in an extended geometric morph paradigm. We find that long-timescale changes in population activity occur orthogonally to the representation of context in network space, allowing for consistent readout of contextual information across weeks. This population-level structure is supported by heterogeneous patterns of activity at the level of individual cells, where we observe evidence of a positive relationship between interpretable contextual coding and long-term stability. Together, these results demonstrate that long-timescale changes to the CA1 spatial code preserve the relative structure of contextual representation.
Expanding beaver pond distribution in Arctic Alaska, 1949 to 2019
Authors: Tape Ken D. , Clark Jason A. , Jones Benjamin M. , Kantner Seth , Gaglioti Benjamin V. , Grosse Guido , Nitze Ingmar 
Published: May 2022

AbstractBeavers were not previously recognized as an Arctic species, and their engineering in the tundra is considered negligible. Recent findings suggest that beavers have moved into Arctic tundra regions and are controlling surface water dynamics, which strongly influence permafrost and landscape stability. Here we use 70 years of satellite images and aerial photography to show the scale and magnitude of northwestward beaver expansion in Alaska, indicated by the construction of over 10,000 beaver ponds in the Arctic tundra. The number of beaver ponds doubled in most areas between ~ 2003 and ~ 2017. Earlier stages of beaver engineering are evident in ~ 1980 imagery, and there is no evidence of beaver engineering in ~ 1952 imagery, consistent with observations from Indigenous communities describing the influx of beavers over the period. Rapidly expanding beaver engineering has created a tundra disturbance regime that appears to be thawing permafrost and exacerbating the effects of climate change.
Adverse events associated with JAK inhibitors in 126,815 reports from the WHO pharmacovigilance database
Authors: Hoisnard Léa , Lebrun-Vignes Bénédicte , Maury Sébastien , Mahevas Matthieu , El Karoui Khalil , Roy Lydia , Zarour Anissa , Michel Marc , Cohen José L. , Amiot Aurélien , Claudepierre Pascal , Wolkenstein Pierre , Grimbert Philippe , Sbidian Emilie 
Published: May 2022

AbstractIncreasing number of Janus kinase (JAK) inhibitors have been approved for chronic haematopoietic neoplasms and inflammatory/autoimmune diseases. We aimed to assess safety of the first three approved JAK inhibitors: ruxolitinib, tofacitinib and baricitinib. In this retrospective observational study, pharmacovigilance data were extracted from the World Health Organization database. Adverse events are classified according to Medical Dictionary for Regulatory Activities hierarchy. Until February 28, 2021, all Individual Case Safety Reports [ICSRs] with the suspected drug ruxolitinib, tofacitinib or baricitinib were included. Disproportionality analysis was performed and the information component (IC) was estimated. Adverse events were considered a significant signal if the lower end of the 95% credibility interval of the IC (IC025) was positive. We identified 126,815 ICSRs involving JAK inhibitors. Ruxolitinib, tofacitinib and baricitinib were associated with infectious adverse events (IC025 1.7, especially with viral [herpes and influenza], fungal, and mycobacterial infectious disorders); musculoskeletal and connective tissue disorders (IC025 1.1); embolism and thrombosis (IC025 0.4); and neoplasms (IC025 0.8, especially malignant skin neoplasms). Tofacitinib was associated with gastrointestinal perforation events (IC025 1.5). We did not find a significant increase in the reporting of major cardiovascular events. We identified significant association between adverse events and ruxolitinib, tofacinitib and baricitinib in international pharmacovigilance database.
Electrical mapping of thermoelectric power factor in WO3 thin film
Authors: Shimizu Sunao , Kishi Tomoya , Ogane Goki , Tokiwa Kazuyasu , Ono Shimpei 
Published: May 2022

AbstractWith growing environmental awareness and considerable research investment in energy saving, the concept of energy harvesting has become a central topic in the field of materials science. The thermoelectric energy conversion, which is a classic physical phenomenon, has emerged as an indispensable thermal management technology. In addition to conventional experimental investigations of thermoelectric materials, seeking promising materials or structures using computer-based approaches such as machine learning has been considered to accelerate research in recent years. However, the tremendous experimental efforts required to evaluate materials may hinder us from reaping the benefits of the fast-developing computer technology. In this study, an electrical mapping of the thermoelectric power factor is performed in a wide temperature-carrier density regime. An ionic gating technique is applied to an oxide semiconductor WO3, systematically controlling the carrier density to induce a transition from an insulating to a metallic state. Upon electrically scanning the thermoelectric properties, it is demonstrated that the thermoelectric performance of WO3 is optimized at a highly degenerate metallic state. This approach is convenient and applicable to a variety of materials, thus prompting the development of novel functional materials with desirable thermoelectric properties.
COVID-19 patient serum less potently inhibits ACE2-RBD binding for various SARS-CoV-2 RBD mutants
Authors: Junker Daniel , Dulovic Alex , Becker Matthias , Wagner Teresa R. , Kaiser Philipp D. , Traenkle Bjoern , Kienzle Katharina , Bunk Stefanie , Struemper Carlotta , Haeberle Helene , Schmauder Kristina , Ruetalo Natalia , Malek Nisar , Althaus Karina , Koeppen Michael , Rothbauer Ulrich , Walz Juliane S. , Schindler Michael , Bitzer Michael , Göpel Siri , Schneiderhan-Marra Nicole 
Published: May 2022

AbstractAs global vaccination campaigns against SARS-CoV-2 proceed, there is particular interest in the longevity of immune protection, especially with regard to increasingly infectious virus variants. Neutralizing antibodies (Nabs) targeting the receptor binding domain (RBD) of SARS-CoV-2 are promising correlates of protective immunity and have been successfully used for prevention and therapy. As SARS-CoV-2 variants of concern (VOCs) are known to affect binding to the ACE2 receptor and by extension neutralizing activity, we developed a bead-based multiplex ACE2-RBD inhibition assay (RBDCoV-ACE2) as a highly scalable, time-, cost-, and material-saving alternative to infectious live-virus neutralization tests. By mimicking the interaction between ACE2 and the RBD, this serological multiplex assay allows the simultaneous analysis of ACE2 binding inhibition to the RBDs of all SARS-CoV-2 VOCs and variants of interest (VOIs) in a single well. Following validation against a classical virus neutralization test and comparison of performance against a commercially available assay, we analyzed 266 serum samples from 168 COVID-19 patients of varying severity. ACE2 binding inhibition was reduced for ten out of eleven variants examined compared to wild-type, especially for those displaying the E484K mutation such as VOCs beta and gamma. ACE2 binding inhibition, while highly individualistic, positively correlated with IgG levels. ACE2 binding inhibition also correlated with disease severity up to WHO grade 7, after which it reduced.
Statistical optimization for simultaneous removal of methyl red and production of fatty acid methyl esters using fresh alga Scenedesmus obliquus
Authors: El‑Naggar Noura El‑Ahmady , Hamouda Ragaa A. , Abou-El-Souod Ghada W. 
Published: May 2022

AbstractMicroalgae are a diverse group of microorganisms, the majority of which are photosynthetic in nature. Microalgae have different applications, the most important of which is the biological treatment of wastewater. Microalgae grow in various types of wastewater, such as wastewater polluted by Azo dyes, due to microalgae using wastewater as a culture medium, which contains many nutrients like nitrogen, phosphate, and carbon sources. Microalgae grow in various types of wastewater, such as wastewater polluted by Azo dyes, due to microalgae using wastewater as a culture medium, which contains many nutrients like nitrogen, phosphate, and carbon sources. So, microalgae are used for bioremediation of wastewater due to the efficiency of growing in wastewater and for the high production of lipids followed by trans-esterification to biodiesel. Face-centered central composite design (FCCCD) was used to determine the factors that have the most significant impact on the simultaneous decolorization of methyl red and lipid production by the fresh green alga Scenedesmus obliquus. The predicted results indicated that the alga decolorized 70.15% methyl red and produced 20.91% lipids by using 1 g/L nitrogen, an incubation time of 10 days, a pH of 8, and the concentration of methyl red is 17.65 mg/L. The dry biomasses of S. obliquus were also examined by SEM and FTIR before and after treatment with methyl red. SEM and FTIR showed that the properties of dry S. obliquus were altered after the biosorption of methyl red. According to GC–MS analysis of hexane extracts of S. obliquus, the lipid profile differed before and after methyl red decolorization. The results proved that it is possible to use S. obliquus to remove dyes and produce renewable fuels such as biodiesel. The novelty of this study is that this is the first time in which the effect of nitrogen concentrations in the medium used for algal growth on the removal of dye has been studied.
Reliability, usability and identified need for home-based cardiometabolic health self-assessment during the COVID-19 pandemic in Soweto, South Africa
Authors: Calvert Clara , Kolkenbeck-Ruh Andrea , Crouch Simone H. , Soepnel Larske M. , Ware Lisa J. 
Published: May 2022

AbstractA major obstacle to tackling the growing burden of chronic disease in South Africa is lack of testing, particularly where individuals face multiple barriers to accessing health services. We conducted a pilot study to evaluate a cardiometabolic self-measurement kit, including assessment of blood pressure, obesity and urine analysis, amongst adults in Soweto, South Africa. Participants (N = 94) were recruited by researchers during community health screening and were provided with a home test kit including a tablet with self-measurement instructions. The participants entered their results on the tablet and, on completion, the researcher immediately repeated the measurements. We interviewed 10% of participants to understand their experience and views of the kits. Concordance correlation coefficients ranged from 0.78 for waist circumference to 0.93 for height, while the overall percentage agreement ranged from 80.5% for both urine protein and urine glucose testing to 91.4% for the identification of central obesity (ratio of waist circumference to height of ≥ 0.5). Participants saw the need for self-testing and found the process for the most part simple, though urine testing and height self-assessment presented some challenges. This pilot study suggests that self-assessment at home has the potential to facilitate the identification of individuals at risk for cardiometabolic disease in low-income settings, adding to a growing body of evidence on the use of self-testing in disease prevention and detection. However, we would not recommend self-testing for urine glucose and protein without further study.
A network approach to relationships between cannabis use characteristics and psychopathology in the general population
Authors: Betz Linda T. , Penzel Nora , Kambeitz Joseph 
Published: May 2022

AbstractCannabis use characteristics, such as earlier initiation and frequent use, have been associated with an increased risk for developing psychotic experiences and psychotic disorders. However, little is known how these characteristics relate to specific aspects of sub-clinical psychopathology in the general population. Here, we explore the relationships between cannabis use characteristics and psychopathology in a large general population sample (N = 2,544, mean age 29.2 years, 47% women) by employing a network approach. This allows for the identification of unique associations between two cannabis use characteristics (lifetime cumulative frequency of cannabis use, age of cannabis use initiation), and specific psychotic experiences and affective symptoms, while controlling for early risk factors (childhood trauma, urban upbringing). We found particularly pronounced unique positive associations between frequency of cannabis use and specific delusional experiences (persecutory delusions and thought broadcasting). Age of cannabis use initiation was negatively related to visual hallucinatory experiences and irritability, implying that these experiences become more likely the earlier use is initiated. Earlier initiation, but not lifetime frequency of cannabis use, was related to early risk factors. These findings suggest that cannabis use characteristics may contribute differentially to risk for specific psychotic experiences and affective symptoms in the general population.
A high-performance compilation strategy for multiplexing quantum control architecture
Authors: Shan Zheng , Zhu Yu , Zhao Bo 
Published: May 2022

AbstractQuantum computers have already shown significant potential to solve specific problems more efficiently than conventional supercomputers. A major challenge towards noisy intermediate-scale quantum computing is characterizing and reducing the various control costs. Quantum programming describes the process of quantum computation as a sequence, whose elements are selected from a finite set of universal quantum gates. Quantum compilation translates quantum programs to ordered pulses to the quantum control devices subsequently and quantum compilation optimization provides a high-level solution to reduce the control cost efficiently. Here, we propose a high-performance compilation strategy for multiplexing quantum control architecture. For representative benchmarks, the utilization efficiency of control devices increased by 49.44% on average in our work, with an acceptable circuit depth expansion executing on several real superconducting quantum computers of IBM.