bluuebunny/crossref_metadata_2025_split huggingface dataset:
Filopodia rotate and coil by actively generating twist in their actin shaft
Authors: Leijnse Natascha , Barooji Younes Farhangi , Arastoo Mohammad Reza , Sønder Stine Lauritzen , Verhagen Bram , Wullkopf Lena , Erler Janine Terra , Semsey Szabolcs , Nylandsted Jesper , Oddershede Lene Broeng , Doostmohammadi Amin , Bendix Poul Martin 
Published: March 2022

AbstractFilopodia are actin-rich structures, present on the surface of eukaryotic cells. These structures play a pivotal role by allowing cells to explore their environment, generate mechanical forces or perform chemical signaling. Their complex dynamics includes buckling, pulling, length and shape changes. We show that filopodia additionally explore their 3D extracellular space by combining growth and shrinking with axial twisting and buckling. Importantly, the actin core inside filopodia performs a twisting or spinning motion which is observed for a range of cell types spanning from earliest development to highly differentiated tissue cells. Non-equilibrium physical modeling of actin and myosin confirm that twist is an emergent phenomenon of active filaments confined in a narrow channel which is supported by measured traction forces and helical buckles that can be ascribed to accumulation of sufficient twist. These results lead us to conclude that activity induced twisting of the actin shaft is a general mechanism underlying fundamental functions of filopodia.
Programmable design of isothermal nucleic acid diagnostic assays through abstraction-based models
Authors: Xu Gaolian , Reboud Julien , Guo Yunfei , Yang Hao , Gu Hongchen , Fan Chunhai , Qian Xiaohua , Cooper Jonathan M. 
Published: March 2022

AbstractAccelerating the design of nucleic acid amplification methods remains a critical challenge in the development of molecular tools to identify biomarkers to diagnose both infectious and non-communicable diseases. Many of the principles that underpin these mechanisms are often complex and can require iterative optimisation. Here we focus on creating a generalisable isothermal nucleic acid amplification methodology, describing the systematic implementation of abstraction-based models for the algorithmic design and application of assays. We demonstrate the simplicity, ease and flexibility of our approach using a software tool that provides amplification schemes de novo, based upon a user-input target sequence. The abstraction of reaction network predicts multiple reaction pathways across different strategies, facilitating assay optimisation for specific applications, including the ready design of multiplexed tests for short nucleic acid sequence miRNAs or for difficult pathogenic targets, such as highly mutating viruses.
Current-induced Néel order switching facilitated by magnetic phase transition
Authors: Wu Hao , Zhang Hantao , Wang Baomin , Groß Felix , Yang Chao-Yao , Li Gengfei , Guo Chenyang , He Haoran , Wong Kin , Wu Di , Han Xiufeng , Lai Chih-Huang , Gräfe Joachim , Cheng Ran , Wang Kang L. 
Published: March 2022

AbstractTerahertz (THz) spin dynamics and vanishing stray field make antiferromagnetic (AFM) materials the most promising candidate for the next-generation magnetic memory technology with revolutionary storage density and writing speed. However, owing to the extremely large exchange energy barriers, energy-efficient manipulation has been a fundamental challenge in AFM systems. Here, we report an electrical writing of antiferromagnetic orders through a record-low current density on the order of 106 A cm−2 facilitated by the unique AFM-ferromagnetic (FM) phase transition in FeRh. By introducing a transient FM state via current-induced Joule heating, the spin-orbit torque can switch the AFM order parameter by 90° with a reduced writing current density similar to ordinary FM materials. This mechanism is further verified by measuring the temperature and magnetic bias field dependences, where the X-ray magnetic linear dichroism (XMLD) results confirm the AFM switching besides the electrical transport measurement. Our findings demonstrate the exciting possibility of writing operations in AFM-based devices with a lower current density, opening a new pathway towards pure AFM memory applications.
Genetic variation of macronutrient tolerance in Drosophila melanogaster
Authors: Havula E. , Ghazanfar S. , Lamichane N. , Francis D. , Hasygar K. , Liu Y. , Alton L. A. , Johnstone J. , Needham E. J. , Pulpitel T. , Clark T. , Niranjan H. N. , Shang V. , Tong V. , Jiwnani N. , Audia G. , Alves A. N. , Sylow L. , Mirth C. , Neely G. G. , Yang J. , Hietakangas V. , Simpson S. J. , Senior A. M. 
Published: March 2022

AbstractCarbohydrates, proteins and lipids are essential nutrients to all animals; however, closely related species, populations, and individuals can display dramatic variation in diet. Here we explore the variation in macronutrient tolerance in Drosophila melanogaster using the Drosophila genetic reference panel, a collection of ~200 strains derived from a single natural population. Our study demonstrates that D. melanogaster, often considered a “dietary generalist”, displays marked genetic variation in survival on different diets, notably on high-sugar diet. Our genetic analysis and functional validation identify several regulators of macronutrient tolerance, including CG10960/GLUT8, Pkn and Eip75B. We also demonstrate a role for the JNK pathway in sugar tolerance and de novo lipogenesis. Finally, we report a role for tailless, a conserved orphan nuclear hormone receptor, in regulating sugar metabolism via insulin-like peptide secretion and sugar-responsive CCHamide-2 expression. Our study provides support for the use of nutrigenomics in the development of personalized nutrition.
Giant tunable spin Hall angle in sputtered Bi2Se3 controlled by an electric field
Authors: Lu Qi , Li Ping , Guo Zhixin , Dong Guohua , Peng Bin , Zha Xi , Min Tai , Zhou Ziyao , Liu Ming 
Published: March 2022

AbstractFinding an effective way to greatly tune spin Hall angle in a low power manner is of fundamental importance for tunable and energy-efficient spintronic devices. Recently, topological insulator of Bi2Se3, having a large intrinsic spin Hall angle, show great capability to generate strong current-induced spin-orbit torques. Here we demonstrate that the spin Hall angle in Bi2Se3 can be effectively tuned asymmetrically and even enhanced about 600% reversibly by applying a bipolar electric field across the piezoelectric substrate. We reveal that the enhancement of spin Hall angle originates from both the charge doping and piezoelectric strain effet on the spin Berry curvature near Fermi level in Bi2Se3. Our findings provide a platform for achieving low power consumption and tunable spintronic devices.
Monospecific and bispecific monoclonal SARS-CoV-2 neutralizing antibodies that maintain potency against B.1.617
Authors: Peng Lei , Hu Yingxia , Mankowski Madeleine C. , Ren Ping , Chen Rita E. , Wei Jin , Zhao Min , Li Tongqing , Tripler Therese , Ye Lupeng , Chow Ryan D. , Fang Zhenhao , Wu Chunxiang , Dong Matthew B. , Cook Matthew , Wang Guilin , Clark Paul , Nelson Bryce , Klein Daryl , Sutton Richard , Diamond Michael S. , Wilen Craig B. , Xiong Yong , Chen Sidi 
Published: March 2022

AbstractCOVID-19 pathogen SARS-CoV-2 has infected hundreds of millions and caused over 5 million deaths to date. Although multiple vaccines are available, breakthrough infections occur especially by emerging variants. Effective therapeutic options such as monoclonal antibodies (mAbs) are still critical. Here, we report the development, cryo-EM structures, and functional analyses of mAbs that potently neutralize SARS-CoV-2 variants of concern. By high-throughput single cell sequencing of B cells from spike receptor binding domain (RBD) immunized animals, we identify two highly potent SARS-CoV-2 neutralizing mAb clones that have single-digit nanomolar affinity and low-picomolar avidity, and generate a bispecific antibody. Lead antibodies show strong inhibitory activity against historical SARS-CoV-2 and several emerging variants of concern. We solve several cryo-EM structures at ~3 Å resolution of these neutralizing antibodies in complex with prefusion spike trimer ectodomain, and reveal distinct epitopes, binding patterns, and conformations. The lead clones also show potent efficacy in vivo against authentic SARS-CoV-2 in both prophylactic and therapeutic settings. We also generate and characterize a humanized antibody to facilitate translation and drug development. The humanized clone also has strong potency against both the original virus and the B.1.617.2 Delta variant. These mAbs expand the repertoire of therapeutics against SARS-CoV-2 and emerging variants.
Windows of developmental sensitivity to social media
Authors: Orben Amy , Przybylski Andrew K. , Blakemore Sarah-Jayne , Kievit Rogier A. 
Published: March 2022

AbstractThe relationship between social media use and life satisfaction changes across adolescent development. Our analyses of two UK datasets comprising 84,011 participants (10–80 years old) find that the cross-sectional relationship between self-reported estimates of social media use and life satisfaction ratings is most negative in younger adolescents. Furthermore, sex differences in this relationship are only present during this time. Longitudinal analyses of 17,409 participants (10–21 years old) suggest distinct developmental windows of sensitivity to social media in adolescence, when higher estimated social media use predicts a decrease in life satisfaction ratings one year later (and vice-versa: lower estimated social media use predicts an increase in life satisfaction ratings). These windows occur at different ages for males (14–15 and 19 years old) and females (11–13 and 19 years old). Decreases in life satisfaction ratings also predicted subsequent increases in estimated social media use, however, these were not associated with age or sex.
Correlational networking guides the discovery of unclustered lanthipeptide protease-encoding genes
Authors: Xue Dan , Older Ethan A. , Zhong Zheng , Shang Zhuo , Chen Nanzhu , Dittenhauser Nolan , Hou Lukuan , Cai Peiyan , Walla Michael D. , Dong Shi-Hui , Tang Xiaoyu , Chen Hexin , Nagarkatti Prakash , Nagarkatti Mitzi , Li Yong-Xin , Li Jie 
Published: March 2022

AbstractBacterial natural product biosynthetic genes, canonically clustered, have been increasingly found to rely on hidden enzymes encoded elsewhere in the genome for completion of biosynthesis. The study and application of lanthipeptides are frequently hindered by unclustered protease genes required for final maturation. Here, we establish a global correlation network bridging the gap between lanthipeptide precursors and hidden proteases. Applying our analysis to 161,954 bacterial genomes, we establish 5209 correlations between precursors and hidden proteases, with 91 prioritized. We use network predictions and co-expression analysis to reveal a previously missing protease for the maturation of class I lanthipeptide paenilan. We further discover widely distributed bacterial M16B metallopeptidases of previously unclear biological function as a new family of lanthipeptide proteases. We show the involvement of a pair of bifunctional M16B proteases in the production of previously unreported class III lanthipeptides with high substrate specificity. Together, these results demonstrate the strength of our correlational networking approach to the discovery of hidden lanthipeptide proteases and potentially other missing enzymes for natural products biosynthesis.
Fast and selective reduction of nitroarenes under visible light with an earth-abundant plasmonic photocatalyst
Authors: Cheruvathoor Poulose Aby , Zoppellaro Giorgio , Konidakis Ioannis , Serpetzoglou Efthymis , Stratakis Emmanuel , Tomanec Ondřej , Beller Matthias , Bakandritsos Aristides , Zbořil Radek 
Published: March 2022

AbstractReduction of nitroaromatics to the corresponding amines is a key process in the fine and bulk chemicals industry to produce polymers, pharmaceuticals, agrochemicals and dyes. However, their effective and selective reduction requires high temperatures and pressurized hydrogen and involves noble metal-based catalysts. Here we report on an earth-abundant, plasmonic nano-photocatalyst, with an excellent reaction rate towards the selective hydrogenation of nitroaromatics. With solar light as the only energy input, the chalcopyrite catalyst operates through the combined action of hot holes and photothermal effects. Ultrafast laser transient absorption and light-induced electron paramagnetic resonance spectroscopies have unveiled the energy matching of the hot holes in the valence band of the catalyst with the frontier orbitals of the hydrogen and electron donor, via a transient coordination intermediate. Consequently, the reusable and sustainable copper-iron-sulfide (CuFeS2) catalyst delivers previously unattainable turnover frequencies, even in large-scale reactions, while the cost-normalized production rate stands an order of magnitude above the state of the art.
An expert-curated global database of online newspaper articles on spiders and spider bites
Authors: Mammola Stefano , Malumbres-Olarte Jagoba , Arabesky Valeria , Barrales-Alcalá Diego Alejandro , Barrion-Dupo Aimee Lynn , Benamú Marco Antonio , Bird Tharina L. , Bogomolova Maria , Cardoso Pedro , Chatzaki Maria , Cheng Ren-Chung , Chu Tien-Ai , Classen-Rodríguez Leticia M. , Čupić Iva , Dhiya’ulhaq Naufal Urfi , Picard André-Philippe Drapeau , El-Hennawy Hisham K. , Elverici Mert , Fukushima Caroline S. , Ganem Zeana , Gavish-Regev Efrat , Gonnye Naledi T. , Hacala Axel , Haddad Charles R. , Hesselberg Thomas , Ho Tammy Ai Tian , Into Thanakorn , Isaia Marco , Jayaraman Dharmaraj , Karuaera Nanguei , Khalap Rajashree , Khalap Kiran , Kim Dongyoung , Korhonen Tuuli , Kralj-Fišer Simona , Land Heidi , Lin Shou-Wang , Loboda Sarah , Lowe Elizabeth , Lubin Yael , Martínez Alejandro , Mbo Zingisile , Miličić Marija , Kioko Grace Mwende , Nanni Veronica , Norma-Rashid Yusoff , Nwankwo Daniel , Painting Christina J. , Pang Aleck , Pantini Paolo , Pavlek Martina , Pearce Richard , Petcharad Booppa , Pétillon Julien , Raberahona Onjaherizo Christian , Saarinen Joni A. , Segura-Hernández Laura , Sentenská Lenka , Uhl Gabriele , Walker Leilani , Warui Charles M. , Wiśniewski Konrad , Zamani Alireza , Scott Catherine , Chuang Angela 
Published: March 2022

AbstractMass media plays an important role in the construction and circulation of risk perception associated with animals. Widely feared groups such as spiders frequently end up in the spotlight of traditional and social media. We compiled an expert-curated global database on the online newspaper coverage of human-spider encounters over the past ten years (2010–2020). This database includes information about the location of each human-spider encounter reported in the news article and a quantitative characterisation of the content—location, presence of photographs of spiders and bites, number and type of errors, consultation of experts, and a subjective assessment of sensationalism. In total, we collected 5348 unique news articles from 81 countries in 40 languages. The database refers to 211 identified and unidentified spider species and 2644 unique human-spider encounters (1121 bites and 147 as deadly bites). To facilitate data reuse, we explain the main caveats that need to be made when analysing this database and discuss research ideas and questions that can be explored with it.
Sea ice loss of the Barents-Kara Sea enhances the winter warming over the Tibetan Plateau
Authors: Duan Anmin , Peng Yuzhuo , Liu Jiping , Chen Yuhang , Wu Guoxiong , Holland David M. , He Bian , Hu Wenting , Tang Yuheng , Li Xichen 
Published: March 2022

AbstractThe Tibetan Plateau (TP) is known as one of the most sensitive regions to climate change, and it has experienced accelerated warming in recent decades. However, to what degree the TP warming amplification relates to remote forcing such as sea ice loss in the Arctic sea ice remains unclear. Here, we found that the decline of sea ice concentration over the Barents-Kara Sea (BKS) could account for 18–32% of the winter warming over the TP by comparing observational data and ensemble experiments from an atmospheric general circulation model. The reduced BKS sea ice and resultant upward turbulent heat fluxes can intensify a Rossby wave train propagating equatorward to the TP. As a result, the enhanced southwesterlies towards the TP strengthen the warm advection over most parts of the TP and lead to TP warming. In addition, an atmospheric teleconnection between the Arctic and the TP also exists in the interannual variability. That is, a tripole mode in air temperature, with warm centers in the Arctic and TP but a cold center in the mid-high latitudes of the Eurasian continent in between. Our results imply that the BKS sea ice loss could intensify such a tripole mode and thus enhancing the winter TP warming.
Case series of outcomes in advanced cancer patients with single pathway alterations receiving N-of-One therapies
Authors: Gupta Diviya , Kurzrock Razelle , Lee Suzanna , Okamura Ryosuke , Lim Hyo Jeong , Kim Ki Hwan , Sicklick Jason K. , Kato Shumei 
Published: March 2022

AbstractThough advanced cancers generally display complex molecular portfolios, there is a subset of patients whose malignancies possess only one genomic alteration or alterations in one oncogenic pathway. We assess how N-of-One therapeutic strategies impact outcomes in these patients. From 12/2012 to 9/2018, 429 therapy-evaluable patients with diverse treatment-refractory cancers were presented at Molecular Tumor Boards at Moores Cancer Center at UC San Diego. The clinical benefit rate, defined by RECIST1.1, was assessed for patients with solid tumors who underwent next-generation sequencing (NGS) profiling revealing one genomic or pathway alteration, subsequently managed with N-of-One therapies. Nine of 429 patients (2.1%) met evaluation criteria. Using matched therapy indicated by NGS, the clinical benefit rate (stable disease ≥ 6 months/partial/complete response) was 66.7%. Median progression-free survival was 11.3 months (95% CI: 3.4–not evaluable). Thus, a small subset of diverse cancers has single pathway alterations on NGS testing. These patients may benefit from customized therapeutic matching.
Mouse and human antibodies bind HLA-E-leader peptide complexes and enhance NK cell cytotoxicity
Authors: Li Dapeng , Brackenridge Simon , Walters Lucy C. , Swanson Olivia , Harlos Karl , Rozbesky Daniel , Cain Derek W. , Wiehe Kevin , Scearce Richard M. , Barr Maggie , Mu Zekun , Parks Robert , Quastel Max , Edwards Robert J. , Wang Yunfei , Rountree Wes , Saunders Kevin O. , Ferrari Guido , Borrow Persephone , Jones E. Yvonne , Alam S. Munir , Azoitei Mihai L. , Gillespie Geraldine M. , McMichael Andrew J. , Haynes Barton F. 
Published: March 2022

AbstractThe non-classical class Ib molecule human leukocyte antigen E (HLA-E) has limited polymorphism and can bind HLA class Ia leader peptides (VL9). HLA-E-VL9 complexes interact with the natural killer (NK) cell receptors NKG2A-C/CD94 and regulate NK cell-mediated cytotoxicity. Here we report the isolation of 3H4, a murine HLA-E-VL9-specific IgM antibody that enhances killing of HLA-E-VL9-expressing cells by an NKG2A+NK cell line. Structural analysis reveal that 3H4 acts by preventing CD94/NKG2A docking on HLA-E-VL9. Upon in vitro maturation, an affinity-optimized IgG form of 3H4 showes enhanced NK killing of HLA-E-VL9-expressing cells. HLA-E-VL9-specific IgM antibodies similar in function to 3H4 are also isolated from naïve B cells of cytomegalovirus (CMV)-negative, healthy humans. Thus, HLA-E-VL9-targeting mouse and human antibodies isolated from the naïve B cell antibody pool have the capacity to enhance NK cell cytotoxicity.
Co-transcriptional splicing efficiency is a gene-specific feature that can be regulated by TGFβ
Authors: Sánchez-Escabias Elena , Guerrero-Martínez José A. , Reyes José C. 
Published: March 2022

AbstractDifferential splicing efficiency of specific introns is a mechanism that dramatically increases protein diversity, based on selection of alternative exons for the final mature mRNA. However, it is unclear whether splicing efficiency of introns within the same gene is coordinated and eventually regulated as a mechanism to control mature mRNA levels. Based on nascent chromatin-associated RNA-sequencing data, we now find that co-transcriptional splicing (CTS) efficiency tends to be similar between the different introns of a gene. We establish that two well-differentiated strategies for CTS efficiency exist, at the extremes of a gradient: short genes that produce high levels of pre-mRNA undergo inefficient splicing, while long genes with relatively low levels of pre-mRNA have an efficient splicing. Notably, we observe that genes with efficient CTS display a higher level of mature mRNA relative to their pre-mRNA levels. Further, we show that the TGFβ signal transduction pathway regulates the general CTS efficiency, causing changes in mature mRNA levels. Taken together, our data indicate that CTS efficiency is a gene-specific characteristic that can be regulated to control gene expression.
Molecular consequences of SARS-CoV-2 liver tropism
Authors: Wanner Nicola , Andrieux Geoffroy , Badia-i-Mompel Pau , Edler Carolin , Pfefferle Susanne , Lindenmeyer Maja T. , Schmidt-Lauber Christian , Czogalla Jan , Wong Milagros N. , Okabayashi Yusuke , Braun Fabian , Lütgehetmann Marc , Meister Elisabeth , Lu Shun , Noriega Maria L. M. , Günther Thomas , Grundhoff Adam , Fischer Nicole , Bräuninger Hanna , Lindner Diana , Westermann Dirk , Haas Fabian , Roedl Kevin , Kluge Stefan , Addo Marylyn M. , Huber Samuel , Lohse Ansgar W. , Reiser Jochen , Ondruschka Benjamin , Sperhake Jan P. , Saez-Rodriguez Julio , Boerries Melanie , Hayek Salim S. , Aepfelbacher Martin , Scaturro Pietro , Puelles Victor G. , Huber Tobias B. 
Published: March 2022

AbstractExtrapulmonary manifestations of COVID-19 have gained attention due to their links to clinical outcomes and their potential long-term sequelae1. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) displays tropism towards several organs, including the heart and kidney. Whether it also directly affects the liver has been debated2,3. Here we provide clinical, histopathological, molecular and bioinformatic evidence for the hepatic tropism of SARS-CoV-2. We find that liver injury, indicated by a high frequency of abnormal liver function tests, is a common clinical feature of COVID-19 in two independent cohorts of patients with COVID-19 requiring hospitalization. Using autopsy samples obtained from a third patient cohort, we provide multiple levels of evidence for SARS-CoV-2 liver tropism, including viral RNA detection in 69% of autopsy liver specimens, and successful isolation of infectious SARS-CoV-2 from liver tissue postmortem. Furthermore, we identify transcription-, proteomic- and transcription factor-based activity profiles in hepatic autopsy samples, revealing similarities to the signatures associated with multiple other viral infections of the human liver. Together, we provide a comprehensive multimodal analysis of SARS-CoV-2 liver tropism, which increases our understanding of the molecular consequences of severe COVID-19 and could be useful for the identification of organ-specific pharmacological targets.