bluuebunny/crossref_metadata_2025_split huggingface dataset:
Photocrosslinking-induced CRAC channel-like Orai1 activation independent of STIM1
Authors: Maltan Lena , Weiß Sarah , Najjar Hadil , Leopold Melanie , Lindinger Sonja , Höglinger Carmen , Höbarth Lorenz , Sallinger Matthias , Grabmayr Herwig , Berlansky Sascha , Krivic Denis , Hopl Valentina , Blaimschein Anna , Fahrner Marc , Frischauf Irene , Tiffner Adéla , Derler Isabella 
Published: March 2023

AbstractCa2+ release-activated Ca2+ (CRAC) channels, indispensable for the immune system and various other human body functions, consist of two transmembrane (TM) proteins, the Ca2+-sensor STIM1 in the ER membrane and the Ca2+ ion channel Orai1 in the plasma membrane. Here we employ genetic code expansion in mammalian cell lines to incorporate the photocrosslinking unnatural amino acids (UAA), p-benzoyl-L-phenylalanine (Bpa) and p-azido-L-phenylalanine (Azi), into the Orai1 TM domains at different sites. Characterization of the respective UAA-containing Orai1 mutants using Ca2+ imaging and electrophysiology reveal that exposure to UV light triggers a range of effects depending on the UAA and its site of incorporation. In particular, photoactivation at A137 using Bpa in Orai1 activates Ca2+ currents that best match the biophysical properties of CRAC channels and are capable of triggering downstream signaling pathways such as nuclear factor of activated T-cells (NFAT) translocation into the nucleus without the need for the physiological activator STIM1.
Evolutionary conservation of the fidelity of transcription
Authors: Chung Claire , Verheijen Bert M. , Navapanich Zoe , McGann Eric G. , Shemtov Sarah , Lai Guan-Ju , Arora Payal , Towheed Atif , Haroon Suraiya , Holczbauer Agnes , Chang Sharon , Manojlovic Zarko , Simpson Stephen , Thomas Kelley W. , Kaplan Craig , van Hasselt Peter , Timmers Marc , Erie Dorothy , Chen Lin , Gout Jean-Franćois , Vermulst Marc 
Published: March 2023

AbstractAccurate transcription is required for the faithful expression of genetic information. However, relatively little is known about the molecular mechanisms that control the fidelity of transcription, or the conservation of these mechanisms across the tree of life. To address these issues, we measured the error rate of transcription in five organisms of increasing complexity and found that the error rate of RNA polymerase II ranges from 2.9 × 10−6 ± 1.9 × 10−7/bp in yeast to 4.0 × 10−6 ± 5.2 × 10−7/bp in worms, 5.69 × 10−6 ± 8.2 × 10−7/bp in flies, 4.9 × 10−6 ± 3.6 × 10−7/bp in mouse cells and 4.7 × 10−6 ± 9.9 × 10−8/bp in human cells. These error rates were modified by various factors including aging, mutagen treatment and gene modifications. For example, the deletion or modification of several related genes increased the error rate substantially in both yeast and human cells. This research highlights the evolutionary conservation of factors that control the fidelity of transcription. Additionally, these experiments provide a reasonable estimate of the error rate of transcription in human cells and identify disease alleles in a subunit of RNA polymerase II that display error-prone transcription. Finally, we provide evidence suggesting that the error rate and spectrum of transcription co-evolved with our genetic code.
Working memory control dynamics follow principles of spatial computing
Authors: Lundqvist Mikael , Brincat Scott L. , Rose Jonas , Warden Melissa R. , Buschman Timothy J. , Miller Earl K. , Herman Pawel 
Published: March 2023

AbstractWorking memory (WM) allows us to remember and selectively control a limited set of items. Neural evidence suggests it is achieved by interactions between bursts of beta and gamma oscillations. However, it is not clear how oscillations, reflecting coherent activity of millions of neurons, can selectively control individual WM items. Here we propose the novel concept of spatial computing where beta and gamma interactions cause item-specific activity to flow spatially across the network during a task. This way, control-related information such as item order is stored in the spatial activity independent of the detailed recurrent connectivity supporting the item-specific activity itself. The spatial flow is in turn reflected in low-dimensional activity shared by many neurons. We verify these predictions by analyzing local field potentials and neuronal spiking. We hypothesize that spatial computing can facilitate generalization and zero-shot learning by utilizing spatial component as an additional information encoding dimension.
Towards routine chromosome-scale haplotype-resolved reconstruction in cancer genomics
Authors: Garg Shilpa 
Published: March 2023

AbstractCancer genomes are highly complex and heterogeneous. The standard short-read sequencing and analytical methods are unable to provide the complete and precise base-level structural variant landscape of cancer genomes. In this work, we apply high-resolution long accurate HiFi and long-range Hi-C sequencing to the melanoma COLO829 cancer line. Also, we develop an efficient graph-based approach that processes these data types for chromosome-scale haplotype-resolved reconstruction to characterise the cancer precise structural variant landscape. Our method produces high-quality phased scaffolds on the chromosome level on three healthy samples and the COLO829 cancer line in less than half a day even in the absence of trio information, outperforming existing state-of-the-art methods. In the COLO829 cancer cell line, here we show that our method identifies and characterises precise somatic structural variant calls in important repeat elements that were missed in short-read-based call sets. Our method also finds the precise chromosome-level structural variant (germline and somatic) landscape with 19,956 insertions, 14,846 deletions, 421 duplications, 52 inversions and 498 translocations at the base resolution. Our simple pstools approach should facilitate better personalised diagnosis and disease management, including predicting therapeutic responses.
Cobalt-catalyzed enantioselective intramolecular reductive cyclization via electrochemistry
Authors: Gao Shiquan , Wang Chen , Yang Junfeng , Zhang Junliang 
Published: March 2023

AbstractTransition-metal catalyzed asymmetric cyclization of 1,6-enynes has emerged as a powerful method for the construction of carbocycles and heterocycles. However, very rare examples worked under electrochemical conditions. We report herein a Co-catalyzed enantioselective intramolecular reductive coupling of enynes via electrochemistry using H2O as hydride source. The products were obtained in good yields with high regio- and enantioselectivities. It represents the rare progress on the cobalt-catalyzed enantioselective transformation via electrochemistry with a general substrate scope. DFT studies explored the possible reaction pathways and revealed that the oxidative cyclization of enynes by LCo(I) is more favorable than oxidative addition of H2O or other pathways.
Climate-driven tradeoffs between landscape connectivity and the maintenance of the coastal carbon sink
Authors: Valentine Kendall , Herbert Ellen R. , Walters David C. , Chen Yaping , Smith Alexander J. , Kirwan Matthew L. 
Published: March 2023

AbstractEcosystem connectivity tends to increase the resilience and function of ecosystems responding to stressors. Coastal ecosystems sequester disproportionately large amounts of carbon, but rapid exchange of water, nutrients, and sediment makes them vulnerable to sea level rise and coastal erosion. Individual components of the coastal landscape (i.e., marsh, forest, bay) have contrasting responses to sea level rise, making it difficult to forecast the response of the integrated coastal carbon sink. Here we couple a spatially-explicit geomorphic model with a point-based carbon accumulation model, and show that landscape connectivity, in-situ carbon accumulation rates, and the size of the landscape-scale coastal carbon stock all peak at intermediate sea level rise rates despite divergent responses of individual components. Progressive loss of forest biomass under increasing sea level rise leads to a shift from a system dominated by forest biomass carbon towards one dominated by marsh soil carbon that is maintained by substantial recycling of organic carbon between marshes and bays. These results suggest that climate change strengthens connectivity between adjacent coastal ecosystems, but with tradeoffs that include a shift towards more labile carbon, smaller marsh and forest extents, and the accumulation of carbon in portions of the landscape more vulnerable to sea level rise and erosion.
Flexible reuse of cortico-hippocampal representations during encoding and recall of naturalistic events
Authors: Reagh Zachariah M. , Ranganath Charan 
Published: March 2023

AbstractAlthough every life event is unique, there are considerable commonalities across events. However, little is known about whether or how the brain flexibly represents information about different event components at encoding and during remembering. Here, we show that different cortico-hippocampal networks systematically represent specific components of events depicted in videos, both during online experience and during episodic memory retrieval. Regions of an Anterior Temporal Network represented information about people, generalizing across contexts, whereas regions of a Posterior Medial Network represented context information, generalizing across people. Medial prefrontal cortex generalized across videos depicting the same event schema, whereas the hippocampus maintained event-specific representations. Similar effects were seen in real-time and recall, suggesting reuse of event components across overlapping episodic memories. These representational profiles together provide a computationally optimal strategy to scaffold memory for different high-level event components, allowing efficient reuse for event comprehension, recollection, and imagination.
Coseismic fault sealing and fluid pressurization during earthquakes
Authors: Yao Lu , Ma Shengli , Di Toro Giulio 
Published: March 2023

AbstractEarthquakes occur because faults weaken with increasing slip and slip rate. Thermal pressurization (TP) of trapped pore fluids is deemed to be a widespread coseismic fault weakening mechanism. Yet, due to technical challenges, experimental evidence of TP is limited. Here, by exploiting a novel experimental configuration, we simulate seismic slip pulses (slip rate 2.0 m/s) on dolerite-built faults under pore fluid pressures up to 25 MPa. We measure transient sharp weakening, down to almost zero friction and concurrent with a spike in pore fluid pressure, which interrupts the exponential-decay slip weakening. The interpretation of mechanical and microstructural data plus numerical modeling suggests that wear and local melting processes in experimental faults generate ultra-fine materials to seal the pressurized pore water, causing transient TP spikes. Our work suggests that, with wear-induced sealing, TP may also occur in relatively permeable faults and could be quite common in nature.
Vibrational signature of hydrated protons confined in MXene interlayers
Authors: Lounasvuori Mailis , Sun Yangyunli , Mathis Tyler S. , Puskar Ljiljana , Schade Ulrich , Jiang De-En , Gogotsi Yury , Petit Tristan 
Published: March 2023

AbstractThe hydration structure of protons has been studied for decades in bulk water and protonated clusters due to its importance but has remained elusive in planar confined environments. Two-dimensional (2D) transition metal carbides known as MXenes show extreme capacitance in protic electrolytes, which has attracted attention in the energy storage field. We report here that discrete vibrational modes related to protons intercalated in the 2D slits between Ti3C2Tx MXene layers can be detected using operando infrared spectroscopy. The origin of these modes, not observed for protons in bulk water, is attributed to protons with reduced coordination number in confinement based on Density Functional Theory calculations. This study therefore demonstrates a useful tool for the characterization of chemical species under 2D confinement.
Checkpoint kinase 1/2 inhibition potentiates anti-tumoral immune response and sensitizes gliomas to immune checkpoint blockade
Authors: Dmello Crismita , Zhao Junfei , Chen Li , Gould Andrew , Castro Brandyn , Arrieta Victor A. , Zhang Daniel Y. , Kim Kwang-Soo , Kanojia Deepak , Zhang Peng , Miska Jason , Yeeravalli Ragini , Habashy Karl , Saganty Ruth , Kang Seong Jae , Fares Jawad , Liu Connor , Dunn Gavin , Bartom Elizabeth , Schipma Matthew J. , Hsu Patrick D. , Alghamri Mahmoud S. , Lesniak Maciej S. , Heimberger Amy B. , Rabadan Raul , Lee-Chang Catalina , Sonabend Adam M. 
Published: March 2023

AbstractWhereas the contribution of tumor microenvironment to the profound immune suppression of glioblastoma (GBM) is clear, tumor-cell intrinsic mechanisms that regulate resistance to CD8 T cell mediated killing are less understood. Kinases are potentially druggable targets that drive tumor progression and might influence immune response. Here, we perform an in vivo CRISPR screen to identify glioma intrinsic kinases that contribute to evasion of tumor cells from CD8 T cell recognition. The screen reveals checkpoint kinase 2 (Chek2) to be the most important kinase contributing to escape from CD8 T-cell recognition. Genetic depletion or pharmacological inhibition of Chek2 with blood-brain-barrier permeable drugs that are currently being evaluated in clinical trials, in combination with PD-1 or PD-L1 blockade, lead to survival benefit in multiple preclinical glioma models. Mechanistically, loss of Chek2 enhances antigen presentation, STING pathway activation and PD-L1 expression in mouse gliomas. Analysis of human GBMs demonstrates that Chek2 expression is inversely associated with antigen presentation and T-cell activation. Collectively, these results support Chek2 as a promising target for enhancement of response to immune checkpoint blockade therapy in GBM.
Anomalous magnetoresistance by breaking ice rule in Bi2Ir2O7/Dy2Ti2O7 heterostructure
Authors: Zhang Han , Xing Chengkun , Noordhoek Kyle , Liu Zhaoyu , Zhao Tianhao , Horák Lukas , Huang Qing , Hao Lin , Yang Junyi , Pandey Shashi , Dagotto Elbio , Jiang Zhigang , Chu Jiun-Haw , Xin Yan , Choi Eun Sang , Zhou Haidong , Liu Jian 
Published: March 2023

AbstractWhile geometrically frustrated quantum magnets host rich exotic spin states with potentials for revolutionary quantum technologies, most of them are necessarily good insulators which are difficult to be integrated with modern electrical circuit. The grand challenge is to electrically detect the emergent fluctuations and excitations by introducing charge carriers that interact with the localized spins without destroying their collective spin states. Here, we show that, by designing a Bi2Ir2O7/Dy2Ti2O7 heterostructure, the breaking of the spin-ice rule in insulating Dy2Ti2O7 leads to a charge response in the conducting Bi2Ir2O7 measured as anomalous magnetoresistance during the field-induced Kagome ice-to-saturated ice transition. The magnetoresistive anomaly also captures the characteristic angular and temperature dependence of this ice-rule-breaking transition, which has been understood as magnetic monopole condensation. These results demonstrate a novel heteroepitaxial approach for electronically probing the transition between exotic insulating spin states, laying out a blueprint for the metallization of frustrated quantum magnets.
Exciton polariton interactions in Van der Waals superlattices at room temperature
Authors: Zhao Jiaxin , Fieramosca Antonio , Dini Kevin , Bao Ruiqi , Du Wei , Su Rui , Luo Yuan , Zhao Weijie , Sanvitto Daniele , Liew Timothy C. H. , Xiong Qihua 
Published: March 2023

AbstractMonolayer transition-metal dichalcogenide (TMD) materials have attracted a great attention because of their unique properties and promising applications in integrated optoelectronic devices. Being layered materials, they can be stacked vertically to fabricate artificial van der Waals lattices, which offer unique opportunities to tailor the electronic and optical properties. The integration of TMD heterostructures in planar microcavities working in strong coupling regime is particularly important to control the light-matter interactions and form robust polaritons, highly sought for room temperature applications. Here, we demonstrate the systematic control of the coupling-strength by embedding multiple WS2 monolayers in a planar microcavity. The vacuum Rabi splitting is enhanced from 36 meV for one monolayer up to 72 meV for the four-monolayer microcavity. In addition, carrying out time-resolved pump-probe experiments at room temperature we demonstrate the nature of polariton interactions which are dominated by phase space filling effects. Furthermore, we also observe the presence of long-living dark excitations in the multiple monolayer superlattices. Our results pave the way for the realization of polaritonic devices based on planar microcavities embedding multiple monolayers and could potentially lead the way for future devices towards the exploitation of interaction-driven phenomena at room temperature.
The molecular and functional landscape of resistance to immune checkpoint blockade in melanoma
Authors: Lim Su Yin , Shklovskaya Elena , Lee Jenny H. , Pedersen Bernadette , Stewart Ashleigh , Ming Zizhen , Irvine Mal , Shivalingam Brindha , Saw Robyn P. M. , Menzies Alexander M. , Carlino Matteo S. , Scolyer Richard A. , Long Georgina V. , Rizos Helen 
Published: March 2023

AbstractResistance to immune checkpoint inhibitor therapies in melanoma is common and remains an intractable clinical challenge. In this study, we comprehensively profile immune checkpoint inhibitor resistance mechanisms in short-term tumor cell lines and matched tumor samples from melanoma patients progressing on immune checkpoint inhibitors. Combining genome, transcriptome, and high dimensional flow cytometric profiling with functional analysis, we identify three distinct programs of immunotherapy resistance. Here we show that resistance programs include (1) the loss of wild-type antigen expression, resulting from tumor-intrinsic IFNγ signaling and melanoma de-differentiation, (2) the disruption of antigen presentation via multiple independent mechanisms affecting MHC expression, and (3) immune cell exclusion associated with PTEN loss. The dominant role of compromised antigen production and presentation in melanoma resistance to immune checkpoint inhibition highlights the importance of treatment salvage strategies aimed at the restoration of MHC expression, stimulation of innate immunity, and re-expression of wild-type differentiation antigens.
An integrated single cell and spatial transcriptomic map of human white adipose tissue
Authors: Massier Lucas , Jalkanen Jutta , Elmastas Merve , Zhong Jiawei , Wang Tongtong , Nono Nankam Pamela A. , Frendo-Cumbo Scott , Bäckdahl Jesper , Subramanian Narmadha , Sekine Takuya , Kerr Alastair G. , Tseng Ben T. P. , Laurencikiene Jurga , Buggert Marcus , Lourda Magda , Kublickiene Karolina , Bhalla Nayanika , Andersson Alma , Valsesia Armand , Astrup Arne , Blaak Ellen E. , Ståhl Patrik L. , Viguerie Nathalie , Langin Dominique , Wolfrum Christian , Blüher Matthias , Rydén Mikael , Mejhert Niklas 
Published: March 2023

AbstractTo date, single-cell studies of human white adipose tissue (WAT) have been based on small cohort sizes and no cellular consensus nomenclature exists. Herein, we performed a comprehensive meta-analysis of publicly available and newly generated single-cell, single-nucleus, and spatial transcriptomic results from human subcutaneous, omental, and perivascular WAT. Our high-resolution map is built on data from ten studies and allowed us to robustly identify >60 subpopulations of adipocytes, fibroblast and adipogenic progenitors, vascular, and immune cells. Using these results, we deconvolved spatial and bulk transcriptomic data from nine additional cohorts to provide spatial and clinical dimensions to the map. This identified cell-cell interactions as well as relationships between specific cell subtypes and insulin resistance, dyslipidemia, adipocyte volume, and lipolysis upon long-term weight changes. Altogether, our meta-map provides a rich resource defining the cellular and microarchitectural landscape of human WAT and describes the associations between specific cell types and metabolic states.
Correlates of protection and viral load trajectories in omicron breakthrough infections in triple vaccinated healthcare workers
Authors: Marking Ulrika , Havervall Sebastian , Norin Nina Greilert , Bladh Oscar , Christ Wanda , Gordon Max , Ng Henry , Blom Kim , Phillipson Mia , Mangsbo Sara , Alm Jessica J. , Smed-Sörensen Anna , Nilsson Peter , Hober Sophia , Åberg Mikael , Klingström Jonas , Thålin Charlotte 
Published: March 2023

AbstractVaccination offers protection against severe COVID-19 caused by SARS-CoV-2 omicron but is less effective against infection. Characteristics such as serum antibody titer correlation to protection, viral abundance and clearance of omicron infection in vaccinated individuals are scarce. We present a 4-week twice-weekly SARS-CoV-2 qPCR screening in 368 triple vaccinated healthcare workers. Spike-specific IgG levels, neutralization titers and mucosal spike-specific IgA-levels were determined at study start and qPCR-positive participants were sampled repeatedly for two weeks. 81 (cumulative incidence 22%) BA.1, BA.1.1 and BA.2 infections were detected. High serum antibody titers are shown to be protective against infection (p < 0.01), linked to reduced viral load (p < 0.01) and time to viral clearance (p < 0.05). Pre-omicron SARS-CoV-2 infection is independently associated to increased protection against omicron, largely mediated by mucosal spike specific IgA responses (nested models lr test p = 0.02 and 0.008). Only 10% of infected participants remain asymptomatic through the course of their infection. We demonstrate that high levels of vaccine-induced spike-specific WT antibodies are linked to increased protection against infection and to reduced viral load if infected, and suggest that the additional protection offered by pre-omicron SARS-CoV-2 infection largely is mediated by mucosal spike-specific IgA.
Spatial immunization to abate disease spreading in transportation hubs
Authors: Mazzoli Mattia , Gallotti Riccardo , Privitera Filippo , Colet Pere , Ramasco José J. 
Published: March 2023

AbstractProximity social interactions are crucial for infectious diseases transmission. Crowded agglomerations pose serious risk of triggering superspreading events. Locations like transportation hubs (airports and stations) are designed to optimize logistic efficiency, not to reduce crowding, and are characterized by a constant in and out flow of people. Here, we analyze the paradigmatic example of London Heathrow, one of the busiest European airports. Thanks to a dataset of anonymized individuals’ trajectories, we can model the spreading of different diseases to localize the contagion hotspots and to propose a spatial immunization policy targeting them to reduce disease spreading risk. We also detect the most vulnerable destinations to contagions produced at the airport and quantify the benefits of the spatial immunization technique to prevent regional and global disease diffusion. This method is immediately generalizable to train, metro and bus stations and to other facilities such as commercial or convention centers.