bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanical overtone frequency combs
Authors: de Jong Matthijs H. J. , Ganesan Adarsh , Cupertino Andrea , Gröblacher Simon , Norte Richard A.
Published: March 2023

Mechanical frequency combs are poised to bring the applications and utility of optical frequency combs into the mechanical domain. So far, their main challenge has been strict requirements on drive frequencies and power, which complicate operation. We demonstrate a straightforward mechanism to create a frequency comb consisting of mechanical overtones (integer multiples) of a single eigenfrequency, by monolithically integrating a suspended dielectric membrane with a counter-propagating optical trap. The periodic optical field modulates the dielectrophoretic force on the membrane at the overtones of a membrane’s motion. These overtones share a fixed frequency and phase relation, and constitute a mechanical frequency comb. The periodic optical field also creates an optothermal parametric drive that requires no additional power or external frequency reference. This combination of effects results in an easy-to-use mechanical frequency comb platform that requires no precise alignment, no additional feedback or control electronics, and only uses a single, mW continuous wave laser beam. This highlights the overtone frequency comb as the straightforward future for applications in sensing, metrology and quantum acoustics.
Cryptosporidium uses CSpV1 to activate host type I interferon and attenuate antiparasitic defenses
Authors: Deng Silu , He Wei , Gong Ai-Yu , Li Min , Wang Yang , Xia Zijie , Zhang Xin-Tiang , Huang Pacheco Andrew S. , Naqib Ankur , Jenkins Mark , Swanson Patrick C. , Drescher Kristen M. , Strauss-Soukup Juliane K. , Belshan Michael , Chen Xian-Ming
Published: March 2023

Cryptosporidiuminfects gastrointestinal epithelium and is a leading cause of infectious diarrhea and diarrheal-related death in children worldwide. There are no vaccines and no fully effective therapy available for the infection. Type II and III interferon (IFN) responses are important determinants of susceptibility to infection but the role for type I IFN response remains obscure.Cryptosporidium parvumvirus 1 (CSpV1) is a double-stranded RNA (dsRNA) virus harbored byCryptosporidiumspp. Here we show that intestinal epithelial conditionalIfnar1−/−mice (deficient in type I IFN receptor) are resistant toC. parvuminfection. CSpV1-dsRNAs are delivered into host cells and trigger type I IFN response in infected cells. WhereasC. parvuminfection attenuates epithelial response to IFN-γ, loss of type I IFN signaling or inhibition of CSpV1-dsRNA delivery can restore IFN-γ-mediated protective response. Our findings demonstrate that type I IFN signaling in intestinal epithelial cells is detrimental to intestinal anti-C. parvumdefense andCryptosporidiumuses CSpV1 to activate type I IFN signaling to evade epithelial antiparasitic response.
Signature of quantum interference effect in inter-layer Coulomb drag in graphene-based electronic double-layer systems
Authors: Zhu Lijun , Liu Xiaoqiang , Li Lin , Wan Xinyi , Tao Ran , Xie Zhongniu , Feng Ji , Zeng Changgan
Published: March 2023

The distinguishing feature of a quantum system is interference arising from the wave mechanical nature of particles which is clearly central to macroscopic electronic properties. Here, we report the signature of quantum interference effect in inter-layer transport process. Via systematic magneto-drag experiments on graphene-based electronic double-layer systems, we observe low-field correction to the Coulomb-scattering-dominated inter-layer drag resistance in a wide range of temperature and carrier density, with its characteristics sensitive to the band topology of graphene layers. These observations can be attributed to a new type of quantum interference between drag processes, with the interference pathway comprising different carrier diffusion paths in the two constituent conductors. The emergence of such effect relies on the formation of superimposing planar diffusion paths, among which the impurity potentials from intermediate insulating spacer play an essential role. Our findings establish an ideal platform where the interplay between quantum interference and many-body interaction is essential.
B cell class switch recombination is regulated by DYRK1A through MSH6 phosphorylation
Authors: Stoler-Barak Liat , Harris Ethan , Peres Ayelet , Hezroni Hadas , Kuka Mirela , Di Lucia Pietro , Grenov Amalie , Gurwicz Neta , Kupervaser Meital , Yip Bon Ham , Iannacone Matteo , Yaari Gur , Crispino John D. , Shulman Ziv
Published: March 2023

Protection from viral infections depends on immunoglobulin isotype switching, which endows antibodies with effector functions. Here, we find that the protein kinase DYRK1A is essential for B cell-mediated protection from viral infection and effective vaccination through regulation of class switch recombination (CSR). Dyrk1a-deficient B cells are impaired in CSR activity in vivo and in vitro. Phosphoproteomic screens and kinase-activity assays identify MSH6, a DNA mismatch repair protein, as a direct substrate for DYRK1A, and deletion of a single phosphorylation site impaired CSR. After CSR and germinal center (GC) seeding, DYRK1A is required for attenuation of B cell proliferation. These findings demonstrate DYRK1A-mediated biological mechanisms of B cell immune responses that may be used for therapeutic manipulation in antibody-mediated autoimmunity.
Increasing the number of stressors reduces soil ecosystem services worldwide
Authors: Rillig Matthias C. , van der Heijden Marcel G. A. , Berdugo Miguel , Liu Yu-Rong , Riedo Judith , Sanz-Lazaro Carlos , Moreno-Jiménez Eduardo , Romero Ferran , Tedersoo Leho , Delgado-Baquerizo Manuel
Published: March 2023

Increasing the number of environmental stressors could decrease ecosystem functioning in soils. Yet this relationship has not been globally assessed outside laboratory experiments. Here, using two independent global standardized field surveys, and a range of natural and human factors, we test the relationship between the number of environmental stressors exceeding different critical thresholds and the maintenance of multiple ecosystem services across biomes. Our analysis shows that having multiple stressors, from medium levels (>50%), negatively and significantly correlates with impacts on ecosystem services and that having multiple stressors crossing a high-level critical threshold (over 75% of maximum observed levels) reduces soil biodiversity and functioning globally. The number of environmental stressors exceeding the >75% threshold was consistently seen as an important predictor of multiple ecosystem services, therefore improving prediction of ecosystem functioning. Our findings highlight the need to reduce the dimensionality of the human footprint on ecosystems to conserve biodiversity and function.
Partner choice, confounding and trait convergence all contribute to phenotypic partner similarity
Authors: Sjaarda Jennifer , Kutalik Zoltán
Published: March 2023

Partners are often similar in terms of their physical and behavioural traits, such as their education, political affiliation and height. However, it is currently unclear what exactly causes this similarity—partner choice, partner influence increasing similarity over time or confounding factors such as shared environment or indirect assortment. Here, we applied Mendelian randomization to the data of 51,664 couples in the UK Biobank and investigated partner similarity in 118 traits. We found evidence of partner choice for 64 traits, 40 of which had larger phenotypic correlation than causal effect. This suggests that confounders contribute to trait similarity, among which household income, overall health rating and education accounted for 29.8, 14.1 and 11.6% of correlations between partners, respectively. Finally, mediation analysis revealed that most causal associations between different traits in the two partners are indirect. In summary, our results show the mechanisms through which indirect assortment increases the observed partner similarity.
Multiomic analysis of malignant pleural mesothelioma identifies molecular axes and specialized tumor profiles driving intertumor heterogeneity
Authors: Mangiante Lise , Alcala Nicolas , Sexton-Oates Alexandra , Di Genova Alex , Gonzalez-Perez Abel , Khandekar Azhar , Bergstrom Erik N. , Kim Jaehee , Liu Xiran , Blazquez-Encinas Ricardo , Giacobi Colin , Le Stang Nolwenn , Boyault Sandrine , Cuenin Cyrille , Tabone-Eglinger Severine , Damiola Francesca , Voegele Catherine , Ardin Maude , Michallet Marie-Cecile , Soudade Lorraine , Delhomme Tiffany M. , Poret Arnaud , Brevet Marie , Copin Marie-Christine , Giusiano-Courcambeck Sophie , Damotte Diane , Girard Cecile , Hofman Veronique , Hofman Paul , Mouroux Jérôme , Cohen Charlotte , Lacomme Stephanie , Mazieres Julien , de Montpreville Vincent Thomas , Perrin Corinne , Planchard Gaetane , Rousseau Nathalie , Rouquette Isabelle , Sagan Christine , Scherpereel Arnaud , Thivolet Francoise , Vignaud Jean-Michel , Jean Didier , Ilg Anabelle Gilg Soit , Olaso Robert , Meyer Vincent , Boland-Auge Anne , Deleuze Jean-Francois , Altmuller Janine , Nuernberg Peter , Ibáñez-Costa Alejandro , Castaño Justo P. , Lantuejoul Sylvie , Ghantous Akram , Maussion Charles , Courtiol Pierre , Hernandez-Vargas Hector , Caux Christophe , Girard Nicolas , Lopez-Bigas Nuria , Alexandrov Ludmil B. , Galateau-Salle Françoise , Foll Matthieu , Fernandez-Cuesta Lynnette
Published: March 2023

Malignant pleural mesothelioma (MPM) is an aggressive cancer with rising incidence and challenging clinical management. Through a large series of whole-genome sequencing data, integrated with transcriptomic and epigenomic data using multiomics factor analysis, we demonstrate that the current World Health Organization classification only accounts for up to 10% of interpatient molecular differences. Instead, the MESOMICS project paves the way for a morphomolecular classification of MPM based on four dimensions: ploidy, tumor cell morphology, adaptive immune response and CpG island methylator profile. We show that these four dimensions are complementary, capture major interpatient molecular differences and are delimited by extreme phenotypes that—in the case of the interdependent tumor cell morphology and adapted immune response—reflect tumor specialization. These findings unearth the interplay between MPM functional biology and its genomic history, and provide insights into the variations observed in the clinical behavior of patients with MPM.
Exhausted intratumoral Vδ2− γδ T cells in human kidney cancer retain effector function
Authors: Rancan Chiara , Arias-Badia Marcel , Dogra Pranay , Chen Brandon , Aran Dvir , Yang Hai , Luong Diamond , Ilano Arielle , Li Jacky , Chang Hewitt , Kwek Serena S. , Zhang Li , Lanier Lewis L. , Meng Maxwell V. , Farber Donna L. , Fong Lawrence
Published: March 2023

Gamma delta (γδ) T cells reside within human tissues including tumors, but their function in mediating antitumor responses to immune checkpoint inhibition is unknown. Here we show that kidney cancers are infiltrated by Vδ2− γδ T cells, with equivalent representation of Vδ1+ and Vδ1− cells, that are distinct from γδ T cells found in normal human tissues. These tumor-resident Vδ2− T cells can express the transcriptional program of exhausted αβ CD8+ T cells as well as canonical markers of terminal T-cell exhaustion including PD-1, TIGIT and TIM-3. Although Vδ2− γδ T cells have reduced IL-2 production, they retain expression of cytolytic effector molecules and co-stimulatory receptors such as 4-1BB. Exhausted Vδ2− γδ T cells are composed of three distinct populations that lack TCF7, are clonally expanded and express cytotoxic molecules and multiple Vδ2− T-cell receptors. Human tumor-derived Vδ2− γδ T cells maintain cytotoxic function and pro-inflammatory cytokine secretion in vitro. The transcriptional program of Vδ2− T cells in pretreatment tumor biopsies was used to predict subsequent clinical responses to PD-1 blockade in patients with cancer. Thus, Vδ2− γδ T cells within the tumor microenvironment can contribute to antitumor efficacy.
Preclinical models for prediction of immunotherapy outcomes and immune evasion mechanisms in genetically heterogeneous multiple myeloma
Authors: Larrayoz Marta , Garcia-Barchino Maria J. , Celay Jon , Etxebeste Amaia , Jimenez Maddalen , Perez Cristina , Ordoñez Raquel , Cobaleda Cesar , Botta Cirino , Fresquet Vicente , Roa Sergio , Goicoechea Ibai , Maia Catarina , Lasaga Miren , Chesi Marta , Bergsagel P. Leif , Larrayoz Maria J. , Calasanz Maria J. , Campos-Sanchez Elena , Martinez-Cano Jorge , Panizo Carlos , Rodriguez-Otero Paula , Vicent Silvestre , Roncador Giovanna , Gonzalez Patricia , Takahashi Satoru , Katz Samuel G. , Walensky Loren D. , Ruppert Shannon M. , Lasater Elisabeth A. , Amann Maria , Lozano Teresa , Llopiz Diana , Sarobe Pablo , Lasarte Juan J. , Planell Nuria , Gomez-Cabrero David , Kudryashova Olga , Kurilovich Anna , Revuelta Maria V. , Cerchietti Leandro , Agirre Xabier , San Miguel Jesus , Paiva Bruno , Prosper Felipe , Martinez-Climent Jose A.
Published: March 2023

The historical lack of preclinical models reflecting the genetic heterogeneity of multiple myeloma (MM) hampers the advance of therapeutic discoveries. To circumvent this limitation, we screened mice engineered to carry eight MM lesions (NF-κB, KRAS, MYC, TP53, BCL2, cyclin D1, MMSET/NSD2 and c-MAF) combinatorially activated in B lymphocytes following T cell-driven immunization. Fifteen genetically diverse models developed bone marrow (BM) tumors fulfilling MM pathogenesis. Integrative analyses of ∼500 mice and ∼1,000 patients revealed a common MAPK–MYC genetic pathway that accelerated time to progression from precursor states across genetically heterogeneous MM. MYC-dependent time to progression conditioned immune evasion mechanisms that remodeled the BM microenvironment differently. Rapid MYC-driven progressors exhibited a high number of activated/exhausted CD8+ T cells with reduced immunosuppressive regulatory T (Treg) cells, while late MYC acquisition in slow progressors was associated with lower CD8+ T cell infiltration and more abundant Treg cells. Single-cell transcriptomics and functional assays defined a high ratio of CD8+ T cells versus Treg cells as a predictor of response to immune checkpoint blockade (ICB). In clinical series, high CD8+ T/Treg cell ratios underlie early progression in untreated smoldering MM, and correlated with early relapse in newly diagnosed patients with MM under Len/Dex therapy. In ICB-refractory MM models, increasing CD8+ T cell cytotoxicity or depleting Treg cells reversed immunotherapy resistance and yielded prolonged MM control. Our experimental models enable the correlation of MM genetic and immunological traits with preclinical therapy responses, which may inform the next-generation immunotherapy trials.
Multiomic neuropathology improves diagnostic accuracy in pediatric neuro-oncology
Authors: Sturm Dominik , Capper David , Andreiuolo Felipe , Gessi Marco , Kölsche Christian , Reinhardt Annekathrin , Sievers Philipp , Wefers Annika K. , Ebrahimi Azadeh , Suwala Abigail K. , Gielen Gerrit H. , Sill Martin , Schrimpf Daniel , Stichel Damian , Hovestadt Volker , Daenekas Bjarne , Rode Agata , Hamelmann Stefan , Previti Christopher , Jäger Natalie , Buchhalter Ivo , Blattner-Johnson Mirjam , Jones Barbara C. , Warmuth-Metz Monika , Bison Brigitte , Grund Kerstin , Sutter Christian , Hirsch Steffen , Dikow Nicola , Hasselblatt Martin , Schüller Ulrich , Koch Arend , Gerber Nicolas U. , White Christine L. , Buntine Molly K. , Kinross Kathryn , Algar Elizabeth M. , Hansford Jordan R. , Gottardo Nicholas G. , Schuhmann Martin U. , Thomale Ulrich W. , Hernáiz Driever Pablo , Gnekow Astrid , Witt Olaf , Müller Hermann L. , Calaminus Gabriele , Fleischhack Gudrun , Kordes Uwe , Mynarek Martin , Rutkowski Stefan , Frühwald Michael C. , Kramm Christof M. , von Deimling Andreas , Pietsch Torsten , Sahm Felix , Pfister Stefan M. , Jones David. T. W.
Published: March 2023

The large diversity of central nervous system (CNS) tumor types in children and adolescents results in disparate patient outcomes and renders accurate diagnosis challenging. In this study, we prospectively integrated DNA methylation profiling and targeted gene panel sequencing with blinded neuropathological reference diagnostics for a population-based cohort of more than 1,200 newly diagnosed pediatric patients with CNS tumors, to assess their utility in routine neuropathology. We show that the multi-omic integration increased diagnostic accuracy in a substantial proportion of patients through annotation to a refining DNA methylation class (50%), detection of diagnostic or therapeutically relevant genetic alterations (47%) or identification of cancer predisposition syndromes (10%). Discrepant results by neuropathological WHO-based and DNA methylation-based classification (30%) were enriched in histological high-grade gliomas, implicating relevance for current clinical patient management in 5% of all patients. Follow-up (median 2.5 years) suggests improved survival for patients with histological high-grade gliomas displaying lower-grade molecular profiles. These results provide preliminary evidence of the utility of integrating multi-omics in neuropathology for pediatric neuro-oncology.
Establishing an RNA fusions panel in soft tissue sarcoma with clinical validation
Authors: Huang Xiaoqiang , Li Guibin , Li Linghua , Wang Jian , Shen Jianru , Chen Yao , Yu Wuzhong , Chen Ailin , Wu Tao , Ma Ji , Ling Bao , He Liang , Chen Xudan
Published: March 2023

The diagnosis and classification of soft tissue sarcomas (STS) remain challenging because of the rarity and overlapping morphologic manifestations of diverse STS subtypes. Characteristic gene fusions are commonly detected in STS and represent useful diagnostic markers. This study established and validated a custom-designed RNA sequencing panel that identified 64 gene fusions in STS. The analytical performance validation yielded excellent accuracy, with 100% (95% CI, 94.40%-100%) sensitivity and 93.33% (95% CI, 68.05%-99.83%) specificity. Clinical performances were further confirmed with 145 clinical formalin-fixed and paraffin-embedded (FFPE) samples from STS patients. Fusions were detected in 40% of samples (58/145). The common fusions SS18-SSX family, EWSR1-related fusions, COL1A1-PDGFB, FOXO1-associated fusions, and FUS-associated fusions were identified in corresponding STS subtypes. The RNA panel detected specific fusions in several cases where no conclusive diagnosis can be made based on the morphology and immunohistochemistry results. Data collected in this study demonstrate that the RNA fusions panel can better classify STS subtypes and serve as a good supplement for histopathology, exhibiting a great potential for the STS precise diagnosis.
The propensity to sign-track is associated with externalizing behavior and distinct patterns of reward-related brain activation in youth
Authors: Colaizzi Janna M. , Flagel Shelly B. , Gearhardt Ashley N. , Borowitz Michelle A. , Kuplicki Rayus , Zotev Vadim , Clark Grace , Coronado Jennifer , Abbott Talia , Paulus Martin P.
Published: March 2023

Externalizing behaviors in childhood often predict impulse control disorders in adulthood; however, the underlying bio-behavioral risk factors are incompletely understood. In animals, the propensity to sign-track, or the degree to which incentive motivational value is attributed to reward cues, is associated with externalizing-type behaviors and deficits in executive control. Using a Pavlovian conditioned approach paradigm, we quantified sign-tracking in 40 healthy 9–12-year-olds. We also measured parent-reported externalizing behaviors and anticipatory neural activations to outcome-predicting cues using the monetary incentive delay fMRI task. Sign-tracking was associated with attentional and inhibitory control deficits and the degree of amygdala, but not cortical, activation during reward anticipation. These findings support the hypothesis that youth with a propensity to sign-track are prone to externalizing tendencies, with an over-reliance on subcortical cue-reactive brain systems. This research highlights sign-tracking as a promising experimental approach delineating the behavioral and neural circuitry of individuals at risk for externalizing disorders.
A smart and flexible approach for aggregation of adjacent polygons to meet a minimum target area or attribute value
Authors: Schiavina Marcello , Melchiorri Michele , Freire Sérgio
Published: March 2023

Many geospatial analyses require flexible aggregation of adjacent units to meet a minimum target area or attribute value. This is usually accomplished using several non-automated and complex GIS tasks. We developed an integrated user-friendly approach and algorithm implemented in the ‘GHS-SmartDissolve’ tool, which addresses minimum mapping unit or attribute value requirements, layers resolution mismatch, spatial uncertainty or modifiable areal unit problem in GIScience. This method automatically dissolves adjacent features updating fields’ values to reach a minimum target area or attribute value, using a flexible settings framework to meet user requirements. Also provided as a toolbox for ArcGIS (Esri), the approach is demonstrated by (i) estimating the mean particulate matter concentrations for all municipalities in Italy in 2011 by combining a coarse grid of global PM2.5 concentrations with fine administrative units; (ii) estimating boundaries of Metropolitan areas in Portugal as aggregation of municipalities, by matching their total population.
Non-alcoholic fatty liver disease is associated with decreased bone mineral density in upper Egyptian patients
Authors: Hassan Amro M. , Haridy Mustafa Ahmed , Shoaeir Mohamed Z. , Abdel-Aziz Tarek M. , Qura Mohamed Khairy , Kenawy Eglal M. , Mansour Tarek Mohamed M. , Salaheldin Elsayed Sameh , Ali Wael Esmat , Abdelmeguid Mona Mohamed , Abdel-Gawad Muhammad
Published: March 2023

Nonalcoholic fatty liver disease (NAFLD) has been linked with a number of extra hepatic diseases and could be a potential risk factor of decreasing bone mineral density. To determine whether Upper Egyptian patients with NAFLD are at risk of developing osteoporosis. Cross sectional study was done on a total 100 individuals; 50 patients diagnosed with NAFLD (based on ultrasound imaging) crossed-matched with 50 individuals without NAFLD based on age, sex and body mass index. Bone mineral density, serum calcium and phosphorus levels, serum parathyroid hormone, serum vitamin D and fasting insulin level were assessed. Osteoporosis was prevalent in NAFLD patients versus to controls (19/50 vs. 0/50; P < 0.001). There was significant decrease in bone mineral density in NAFLD patients than controls (− 2.29 ± 0.4 vs. − 1.53 ± 0.1; P < 0.001). There was a statistical significance decrease in serum vitamin D and calcium levels in NAFLD patients than controls. Furthermore, vitamin D levels in the NAFLD group was a predictor for osteoporosis (OR 0.614; 95% CI 0.348–0.825). Patients with NAFLD tend to have a significant decrease in bone density, vitamin D, and serum calcium levels than controls.
Critically synchronized brain waves form an effective, robust and flexible basis for human memory and learning
Authors: Galinsky Vitaly L. , Frank Lawrence R.
Published: March 2023

The effectiveness, robustness, and flexibility of memory and learning constitute the very essence of human natural intelligence, cognition, and consciousness. However, currently accepted views on these subjects have, to date, been put forth without any basis on a true physical theory of how the brain communicates internally via its electrical signals. This lack of a solid theoretical framework has implications not only for our understanding of how the brain works, but also for wide range of computational models developed from the standard orthodox view of brain neuronal organization and brain network derived functioning based on the Hodgkin–Huxley ad-hoc circuit analogies that have produced a multitude of Artificial, Recurrent, Convolution, Spiking, etc., Neural Networks (ARCSe NNs) that have in turn led to the standard algorithms that form the basis of artificial intelligence (AI) and machine learning (ML) methods. Our hypothesis, based upon our recently developed physical model of weakly evanescent brain wave propagation (WETCOW) is that, contrary to the current orthodox model that brain neurons just integrate and fire under accompaniment of slow leaking, they can instead perform much more sophisticated tasks of efficient coherent synchronization/desynchronization guided by the collective influence of propagating nonlinear near critical brain waves, the waves that currently assumed to be nothing but inconsequential subthreshold noise. In this paper we highlight the learning and memory capabilities of our WETCOW framework and then apply it to the specific application of AI/ML and Neural Networks. We demonstrate that the learning inspired by these critically synchronized brain waves is shallow, yet its timing and accuracy outperforms deep ARCSe counterparts on standard test datasets. These results have implications for both our understanding of brain function and for the wide range of AI/ML applications.
A urine-based ELISA with recombinant non-glycosylated SARS-CoV-2 spike protein for detecting anti-SARS-CoV-2 spike antibodies
Authors: Ramos Fernanda F. , Bagno Flávia F. , Vassallo Paula F. , Oliveira-da-Silva João A. , Reis Thiago A. R. , Bandeira Raquel S. , Machado Amanda S. , Lage Daniela P. , Martins Vivian T. , Fernandes Ana P. , Christodoulides Myron , Ravetti Cecilia G. , Nobre Vandack , da Fonseca Flávio G. , Coelho Eduardo A. F. , Ludolf Fernanda
Published: March 2023

Serological assays have been widely used to detect anti-SARS-CoV-2 antibodies, which are generated from previous exposure to the virus or after vaccination. The presence of anti-SARS-CoV-2 Nucleocapsid antibodies was recently reported in patients´ urine using an in-house urine-based ELISA-platform, allowing a non-invasive way to collect clinical samples and assess immune conversion. In the current study, we evaluated and validated another in-house urine-based ELISA for the detection of anti-SARS-CoV-2 Spike antibodies. Three partial recombinant SARS-CoV-2 Spike proteins comprising the Receptor Binding Domain, expressed in eukaryotic or prokaryotic systems, were tested in an ELISA platform against a panel of over 140 urine and paired serum samples collected from 106 patients confirmed positive for SARS-CoV-2 by qRT-PCR. The key findings from our study were that anti-SARS-CoV-2 Spike antibodies could be detected in urine samples and that the prokaryotic expression of the rSARS-CoV-2 Spike protein was not a barrier to obtain relatively high serology efficiency for the urine-based assay. Thus, use of a urine-based ELISA assay with partial rSARS-CoV-2 Spike proteins, expressed in a prokaryotic system, could be considered as a convenient tool for screening for the presence of anti-SARS-CoV-2 Spike antibodies, and overcome the difficulties arising from sample collection and the need for recombinant proteins produced with eukaryotic expression systems.
From a genome-wide screen of RNAi molecules against SARS-CoV-2 to a validated broad-spectrum and potent prophylaxis
Authors: Yogev Ohad , Weissbrod Omer , Battistoni Giorgia , Bressan Dario , Naamati Adi , Falciatori Ilaria , Berkyurek Ahmet Can , Rasnic Roni , Izuagbe Rhys , Hosmillo Myra , Ilan Shaul , Grossman Iris , McCormick Lauren , Honeycutt Christopher Cole , Johnston Timothy , Gagne Matthew , Douek Daniel C , Goodfellow Ian , Hannon Gregory James , Erlich Yaniv
Published: March 2023

Expanding the arsenal of prophylactic approaches against SARS-CoV-2 is of utmost importance, specifically those strategies that are resistant to antigenic drift in Spike. Here, we conducted a screen of over 16,000 RNAi triggers against the SARS-CoV-2 genome, using a massively parallel assay to identify hyper-potent siRNAs. We selected Ten candidates for in vitro validation and found five siRNAs that exhibited hyper-potent activity (IC50 < 20 pM) and strong blockade of infectivity in live-virus experiments. We further enhanced this activity by combinatorial pairing of the siRNA candidates and identified cocktails that were active against multiple types of variants of concern (VOC). We then examined over 2,000 possible mutations in the siRNA target sites by using saturation mutagenesis and confirmed broad protection of the leading cocktail against future variants. Finally, we demonstrated that intranasal administration of this siRNA cocktail effectively attenuates clinical signs and viral measures of disease in the gold-standard Syrian hamster model. Our results pave the way for the development of an additional layer of antiviral prophylaxis that is orthogonal to vaccines and monoclonal antibodies.
Distinct inter-domain interactions of dimeric versus monomeric α-catenin link cell junctions to filaments
Authors: Rangarajan Erumbi S. , Smith Emmanuel W. , Izard Tina
Published: March 2023

Attachment between cells is crucial for almost all aspects of the life of cells. These inter-cell adhesions are mediated by the binding of transmembrane cadherin receptors of one cell to cadherins of a neighboring cell. Inside the cell, cadherin binds β-catenin, which interacts with α-catenin. The transitioning of cells between migration and adhesion is modulated by α-catenin, which links cell junctions and the plasma membrane to the actin cytoskeleton. At cell junctions, a single β-catenin/α-catenin heterodimer slips along filamentous actin in the direction of cytoskeletal tension which unfolds clustered heterodimers to form catch bonds with F-actin. Outside cell junctions, α-catenin dimerizes and links the plasma membrane to F-actin. Under cytoskeletal tension, α-catenin unfolds and forms an asymmetric catch bond with F-actin. To understand the mechanism of this important α-catenin function, we determined the 2.7 Å cryogenic electron microscopy (cryoEM) structures of filamentous actin alone and bound to human dimeric α-catenin. Our structures provide mechanistic insights into the role of the α-catenin interdomain interactions in directing α-catenin function and suggest a bivalent mechanism. Further, our cryoEM structure of human monomeric α-catenin provides mechanistic insights into α-catenin autoinhibition. Collectively, our structures capture the initial α-catenin interaction with F-actin before the sensing of force, which is a crucial event in cell adhesion and human disease.
Seasonal and habitat-based variations in vertical export of biogenic sea-ice proxies in Hudson Bay
Authors: Luostarinen Tiia , Weckström Kaarina , Ehn Jens , Kamula Michelle , Burson Amanda , Diaz Aura , Massé Guillaume , McGowan Suzanne , Kuzyk Zou Zou , Heikkilä Maija
Published: March 2023

Despite their wide use in past sea-ice reconstructions, the seasonal, habitat and species-based sources of sedimentary sea-ice proxies are poorly understood. Here, we conduct direct observations of the community composition of diatoms, dinoflagellate cysts and highly branched isoprenoid lipids within the sea ice, water column, sediment traps and sediment surface in the Belcher Islands Archipelago, Hudson Bay throughout spring 2019. We find that Arctic diatom and dinoflagellate cysts species commonly used as sea-ice proxies appear to be only indirectly linked to sea-ice conditions, and that the sediment assemblages of these groups overrepresent summertime pelagic blooms. Species contributing to the diverse sea-ice diatom communities are rare in the sediment. Dinoflagellate cysts form a typical Arctic assemblage in the sediment, although they are virtually absent in the sea ice and water column in spring. We also find that certain highly branched isoprenoid lipids that were previously considered indicators of open water, can be produced in sea-ice. We conclude that contextual knowledge and a multiproxy approach are necessary in reconstruction, encouraging further studies on the sources and controls of sea-ice proxy production in different geographic areas.
Enroute sustainability: metal free C–H bond functionalisation
Authors: Roy Sayan , Panja Subir , Sahoo Sumeet Ranjan , Chatterjee Sagnik , Maiti Debabrata
Published: March 2023

The metal-free C–H functionalisation is providing environmentally benign, cost-effective, sustainable catalytic systems. Comprehensive developments of various metal-free C–H functionalisation reactions are the focal point of this review.
A bimetallic (Ni/Co) metal–organic framework with excellent oxidase-like activity for colorimetric sensing of ascorbic acid
Authors: Wan Jing , Zou Jian-Mei , Zhou Shu-Jing , Pan Feng-Lan , Hua Fei , Zhang Yu-Lan , Nie Jin-Fang , Zhang Yun
Published: March 2023

A novel colorimetric platform was constructed based on the excellent intrinsic oxidase-like activity of a bimetallic Ni/Co-MOF catalyst, which was synthesized by using a simultaneous precipitation and acid etching method with ZIF-67 as the template.
Theoretical design of a photodetector based on a two-dimensional SnSe2/GaP type-II heterostructure
Authors: Wang Jiaxin , Wei Xing , Xuan Jinzhe , Zhang Yan , Fan Jibin , Ni Lei , Yang Yun , Liu Jian , Tian Ye , Ma Shu , Duan Li
Published: March 2023

The effect on the band alignment of SnSe2/GaP heterojunctions was investigated by applying an external electric field and strain perpendicular to the interface between two monolayers of SnSe2 and GaP.
Framework structured Ce2(C2O4)3·10H2O as a pseudocapacitive electrode of a hybrid (asymmetric) supercapacitor (HSC) for large scale energy storage applications
Authors: Singh Mahatim , Mondal Rakesh , Singh Preetam , Sharma Neeraj
Published: March 2023

The electrochemical kinetics of the electrode material plays a crucial role in the development of various energy storage devices such as batteries, supercapacitors, and hybrid supercapacitors.
Description of conformational ensembles of disordered proteins by residue-local probabilities
Authors: Bastida Adolfo , Zúñiga José , Miguel Beatriz , Soler Miguel A.
Published: March 2023

Neighbour-dependent probability expressions describe accurately the conformational ensembles of disordered proteins from short MD trajectories.
Ionogels: recent advances in design, material properties and emerging biomedical applications
Authors: Fan Xiaotong , Liu Siqi , Jia Zhenhua , Koh J. Justin , Yeo Jayven Chee Chuan , Wang Chen-Gang , Surat'man Nayli Erdeanna , Loh Xian Jun , Le Bideau Jean , He Chaobin , Li Zibiao , Loh Teck-Peng
Published: March 2023

This review describes the most recent developments in materials design and the advanced features of ionogels, as well as their emerging biomedical applications.
Screw sense and screw sensibility: communicating information by conformational switching in helical oligomers
Authors: Morris David T. J. , Clayden Jonathan
Published: March 2023

Helical oligomers devoid of configurational chirality can communicate information when an externally induced screw-sense preference propagates through the chain.
Hydrogen economy driven by offshore wind in regional comprehensive economic partnership members
Authors: Zhuang Wennan , Pan Guangsheng , Gu Wei , Zhou Suyang , Hu Qinran , Gu Zhongfan , Wu Zhi , Lu Shuai , Qiu Haifeng
Published: March 2023

Offshore green-hydrogen production: breakthrough in the bottleneck of offshore wind development.
Microbiome–metabolomics analysis reveals the potential effect of verbascoside in alleviating cognitive impairment in db/db mice
Authors: Ran Zheng , Ju Bowei , Cao Lin , Hou Qiang , Wen Limei , Geng Ruoyu , Liao Yucheng , Hu Junping , Yang Jianhua
Published: March 2023

Verbascoside treatment ameliorated cognitive and memory deficits in db/db mice by reshaping the gut microbiome composition, alleviating diabetic metabolic disturbances, enhancing insulin sensitivity, and protecting the synaptic ultrastructure.
Label-free enrichment of human adipose-derived stem cells using a continuous microfluidic sorting cascade
Authors: Lee Lap Man , Klarmann George J. , Haithcock Dustin W. , Wang Yi , Bhatt Ketan H. , Prabhakarpandian Balabhaskar , Pant Kapil , Alvarez Luis M. , Lai Eva
Published: March 2023

Combining inertial and deterministic lateral displacement (DLD) microfluidic sorting to isolate mesenchymal stem cells (MSCs) from human adipose tissue for regenerative medicine applications.
Rh(iii)-catalyzed direct ortho-C–H diarylation of arylsulfoximines with arylsilanes
Authors: Zhang Xiuqi , Zhang Jie , Li Lin , Zhang Fukuan , Luo Xuzhong , Luo Haiqing
Published: March 2023

Established herein is a Rh(iii)-catalyzed direct ortho-C–H diarylation of arylsulfoximine derivatives with diverse environmentally friendly arylsilanes, allowing the synthesis of potentially valuable tricyclic arylsulfoximine derivatives.
Interface engineering of CeO2nanoparticle/Bi2WO6nanosheet nanohybrids with oxygen vacancies for oxygen evolution reactions under alkaline conditions
Authors: Nam Dukhyun , Lee Geunhyeong , Kim Jooheon
Published: March 2023

The oxygen vacancies of catalysts enhance the electrocatalytic activity. CeO2/Bi2WO6is synthesizedviaa hydrothermal reaction and NaBH4reduction.
Alkaline-earth-metal-ion blending enhanced mechanoluminescence of lanthanide ions in MZnOS hosts for stress sensing and anticounterfeiting
Authors: Jia Jingna , Wang Dongyang , Gao Xuwen , Xu Yuqi , Ren Xiaoxuan , Zou Guizheng
Published: March 2023

Mechanoluminescent (ML) materials with highly-efficient and multicolored emission are strongly anticipated in the field of stress sensing and information encryption.
A novel method for correcting the effect of the lens-to-sample distance change on the signal intensity in laser-induced breakdown spectroscopy
Authors: Ling Yongsheng , Wang Yu , Jia Wenbao , Shan Qing , Hei Daqian , Zhang Jiandong , Zhang Zhichao , Wang Zi
Published: March 2023

Laser-induced breakdown spectroscopy (LIBS) is a promising technique for real-time online coal analysis.
Spiers Memorial Lecture: Shielding the active site: a streptavidin superoxide-dismutase chimera as a host protein for asymmetric transfer hydrogenation
Authors: Igareta Nico V. , Tachibana Ryo , Spiess Daniel C. , Peterson Ryan L. , Ward Thomas R.
Published: March 2023

We have evaluated chimeric streptavidin superoxide dismutase C as a scaffold for an asymmetric transfer hydrogenase, incorporating [Cp*Ir(biot-p-L)Cl] as a cofactor.
Electrochemical synthesis of the protected cyclic (1,3;1,6)-β-glucan dodecasaccharide
Authors: Shibuya Akito , Ishisaka Yui , Saito Asuka , Kato Moeko , Manmode Sujit , Komatsu Hiroto , Rahman Md Azadur , Sasaki Norihiko , Itoh Toshiyuki , Nokami Toshiki
Published: March 2023

A protected cyclic (1,3;1,6)-β-glucan dodecasaccharide was synthesized by the electrochemical one-pot dimerisation–cyclisation of a semi-circular hexasaccharide.
Chemo-enzymatic synthesis of chiral 3-substituted tetrahydroquinolines by a sequential biocatalytic cascade and Buchwald–Hartwig cyclization
Authors: Xu Zefei , Feng Jinhui , Yao Peiyuan , Wu Qiaqing , Zhu Dunming
Published: March 2023

A one-pot bienzymatic cascade was developed to synthesize (S)-N-(3-aryl-2-methylpropyl) prop-2-en-1-amines from α,β-unsaturated aldehydes, and 3-substituted tetrahydroquinolines were preparedviaBuchwald–Hartwig amination and deallylation.
AZABODIPY aggregates as a promising electroluminescent material for sustainable NIR OLED applications
Authors: Mróz Wojciech , Squeo Benedetta Maria , Vercelli Barbara , Botta Chiara , Pasini Mariacecilia
Published: March 2023

AZABODIPY with thiophene and phenyl substituents allows electroluminescence in pure NIR to be achieved.
Cesium lead bromide as a colorimetric and fluorometric sensing platform for the selective detection of uric acid
Authors: Saikia Priyankamoni , Nath Jayashree , Dolui Swapan Kumar , Mahanta Sanjeev Pran
Published: March 2023

In this work, a simple and sensitive colorimetric fluorescence sensing probe was designed for the detection of uric acid (UA).
Do chemists control plane packing, i.e. two-dimensional self-assembly, at all scales?
Authors: Chinaud-Chaix Clémence , Marchenko Nataliia , Fernique Thomas , Tricard Simon
Published: March 2023

With the help of mathematics, we rationalize general concepts of self-assembly of molecules, nanoobjects, micron-sized colloids, and even millimetric shapes.
Novel artesunate–pyrimidine-based hybrids with anticancer potential against multidrug-resistant cancer cells
Authors: Koračak Ljiljana , Lupšić Ema , Jovanović Nataša Terzić , Jovanović Mirna , Novakovic Miroslav , Nedialkov Paraskev , Trendafilova Antoaneta , Zlatović Mario , Pešić Milica , Opsenica Igor M.
Published: March 2023

Approach based on hybrid compounds of artesunate and pyrimidine provided novel and promising anticancer agents.
Fluorescent filter paper with pH-responsive carbon dots for the on-site detection of biogenic amines in food
Authors: Yan Jianfeng , Fu Quanbin , Zhang Shikai , Shi Xianbao , Zhang Yuanhong , Hou Juying , Duan Junling , Ai Shiyun
Published: March 2023

A ratiometric fluorescent sensor for eight kinds of biogenic amines was established by facile mixing of pH-responsive carbon dots and Rhodamine B.
Effect of hydration of a room temperature ionic liquid on the cation–cation interaction of UO22+ and NpO2+ ions
Authors: Verma Parveen Kumar , Bhattacharyya Arunasis , Mohapatra Prasanta Kumar
Published: March 2023

Water activity in RTIL plays an important role in deciding the strength of cation–cation interaction (CCI) between Np(V) and U(vi) as evidenced by the vis-NIR spectroscopic and DFT studies of Np(v)–U(vi) CCI in RTIL with different water content.
Total synthesis of bi-magnolignan
Authors: Lu Si-Yuan , Wang Hong-Mei , Feng Na , Ma Ai-Jun
Published: March 2023

The first total synthesis of bi-magnolignan in eight steps from commercially available starting materials has been developed.
Bent-to-planar Si-rhodamines: a distinct rehybridization lights up NIR-II fluorescence for tracking nitric oxide in the Alzheimer's disease brain
Authors: Xu Qingshuang , Zhang Yutao , Zhu Mingming , Yan Chenxu , Mao Wenle , Zhu Wei-Hong , Guo Zhiqian
Published: March 2023

We report a configuration-dependent strategy to construct bent-to-planar NIR-II fluorophores, based on an innovative rehybridization fluorogenic building block, showing promise for illuminating biological events with high spatio-temporal resolutions.
Solar energy driven C–C bond cleavage in a lignin model compound with a D–π–A organic dye-sensitized photoanode
Authors: Kim Saerona , Kang Hyeong Cheol , Chu Chun , Li Shuya , Yoo Kicheon , Wijethunga Udani Kaushalya , Zheng Weiwei , Yoo Chang Geun , Sherman Benjamin D. , Lee Jae-Joon , Leem Gyu
Published: March 2023

This study reports the solar light-driven activation of a bicyclic aminoxyl mediator to achieve C–C bond cleavage of a lignin model compound at room temperature using a donor–π-conjugated bridge–acceptor organic dye-based photoelectrochemical system.
Sustainable porous carbons from tannic acid based KOH activated as high-performance CO2 capture sorbents
Authors: Zhang Yujia , Tian Fengwu , Guo Xiaosha , Bai Miaomiao , Tang Tian , Di Xixi , Wang Wei , Liu Zhifeng , Shao Xianzhao
Published: March 2023

A potentially viable strategy for the fabrication of efficient sorbents for CO2 capture is the use of porous carbons obtained from biomass, which have a large surface area and delicately organized porous structural framework.
An urchin-like Co-doped NiS2/C nanorod array with enriched sulfur vacancies for asymmetric supercapacitors
Authors: Hu Jingjing , Sun Li , Xie Feng , Qu Yaru , Tan Hankun , Zhang Yihe
Published: March 2023

Co-NiS2/C is prepared by one-step carbonization/sulfurization of Co-NiBTC. Its Co-doping, sulfur vacancies, carbon framework, porosity and urchin-like morphology enable active faradaic reactions and enhanced electrochemical performance.
A laser-induced graphene-based flexible and all-carbon organic electrochemical transistor
Authors: Ren Guozhang , Fan Hua , Zhang Linrong , He Shunhao , Zhu Chengcheng , Gao Kun , Zhang Yulong , Wang Junjie , Kang Xing , Song Yaxin , Gong Zhongyan , Li Gongqiang , Lu Gang , Yu Hai-Dong
Published: March 2023

In this study we design and fabricate an all-carbon OECT by using laser-induced graphene (LIG) as the electrode, and high output performances are achieved because of the porous structure on the LIG surface.
HOTAIR as a diagnostic and prognostic biomarker of gastrointestinal cancers: an updated meta-analysis and bioinformatics analysis based on TCGA data
Authors: Yang Jinyou , Xu Shuyu , Wang Shaozhuo , Zou Xuyan , Duan Mingxiu , Zhang Qiaoling , Wang Chao
Published: March 2023

Gastrointestinal cancers are the most common type of cancer affecting humans. High expression of HOX transcript antisense intergenic RNA (HOTAIR), a long noncoding RNA (lncRNA), in various types of different tumors may be associated with poor prognosis. In the present study, we performed a meta-analysis of the relationship between HOTAIR expression and gastrointestinal cancers. Five databases were comprehensively searched for all literature until January 2023. Moreover, the target genes of HOTAIR were predicted by coexpression analysis based on The Cancer Genome Atlas (TCGA) gene expression matrix for six gastrointestinal cancer types. Finally, the mechanism through which HOTAIR affects tumors of the digestive system was systematically reviewed. Our results showed that the high HOTAIR expression group had worse outcomes with a pooled hazard ratio (HR) of 1.56 (95% confidence interval [CI] = 1.38–1.75, P<0.001). Furthermore, HOTAIR was identified as an unfavorable prognostic factor for overall survival (OS) in the esophageal carcinoma (ESCA) and gastric cancer (GC), as the HR were 1.94 and 1.58, respectively. The high correlation between the expression of homeobox C (HOXC) family genes and HOTAIR, with correlation coefficients of 0.863 (HOXC11), 0.664 (HOXC10), 0.645 (HOXC8), and 0.581 (HOXC12). The ‘cell cycle’ pathway and pathways relating to infections, namely ‘herpes simplex virus 1 infection’ and ‘complement and coagulation cascades’ were significantly enriched in Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Also, we perform a systematic review to summarize the related oncogenic mechanism of HOTAIR. In conclusion, the HOTAIR has been identified as a potential prognostic factor in patients with gastrointestinal cancers.
Modulation of chromatin architecture influences the neuronal nucleus through activity-regulated gene expression
Authors: Porter Robert S. , Iwase Shigeki
Published: March 2023

The disruption of chromatin-regulating genes is associated with many neurocognitive syndromes. While most of these genes are ubiquitously expressed across various cell-types, many chromatin regulators act upon activity regulated genes (ARGs) that play central roles in synaptic development and plasticity. Recent literature suggests a link between ARG expression disruption in neurons with the human phenotypes observed in various neurocognitive syndromes. Advances in chromatin biology have demonstrated how chromatin structure, from nucleosome occupancy to higher-order structures such as topologically associated domains, impacts the kinetics of transcription. This review discusses the dynamics of these various levels of chromatin structure and their influence on the expression of ARGs.