bluuebunny/crossref_metadata_2025 huggingface dataset:
Towards routine chromosome-scale haplotype-resolved reconstruction in cancer genomics
Authors: Garg Shilpa
Published: March 2023

Cancer 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

Transition-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

Ecosystem 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

Although 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

Earthquakes 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

The 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

Whereas 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

While 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

Monolayer 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

Resistance 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

To 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

Vaccination 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

Proximity 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.
Submesoscale inverse energy cascade enhances Southern Ocean eddy heat transport
Authors: Zhang Zhiwei , Liu Yuelin , Qiu Bo , Luo Yiyong , Cai Wenju , Yuan Qingguo , Liu Yinxing , Zhang Hong , Liu Hailong , Miao Mingfang , Zhang Jinchao , Zhao Wei , Tian Jiwei
Published: March 2023

Oceanic eddy-induced meridional heat transport (EHT) is an important process in the Southern Ocean heat budget, the variability of which significantly modulates global meridional overturning circulation (MOC) and Antarctic sea-ice extent. Although it is recognized that mesoscale eddies with scales of ~40–300 km greatly contribute to the EHT, the role of submesoscale eddies with scales of ~1–40 km remains unclear. Here, using two state-of-the-art high-resolution simulations (resolutions of 1/48° and 1/24°), we find that submesoscale eddies significantly enhance the total poleward EHT in the Southern Ocean with an enhancement percentage reaching 19–48% in the Antarctic Circumpolar Current band. By comparing the eddy energy budgets between the two simulations, we detect that the primary role of submesoscale eddies is to strengthen mesoscale eddies (and thus their heat transport capability) through inverse energy cascade rather than directly through submesoscale heat fluxes. Due to the submesoscale-mediated enhancement of mesoscale eddies in the 1/48° simulation, the clockwise upper cell and anti-clockwise lower cell of the residual-mean MOC in the Southern Ocean are weakened and strengthened, respectively. This finding identifies a potential route to improve the mesoscale parameterization in climate models for more accurate simulations of the MOC and sea ice variability in the Southern Ocean.
Deacetylation induced nuclear condensation of HP1γ promotes multiple myeloma drug resistance
Authors: Li Xin , Wang Sheng , Xie Ying , Jiang Hongmei , Guo Jing , Wang Yixuan , Peng Ziyi , Hu Meilin , Wang Mengqi , Wang Jingya , Li Qian , Wang Yafei , Liu Zhiqiang
Published: March 2023

Acquired chemoresistance to proteasome inhibitors is a major obstacle in managing multiple myeloma but key regulators and underlying mechanisms still remain to be explored. We find that high level of HP1γ is associated with low acetylation modification in the bortezomib-resistant myeloma cells using SILAC-based acetyl-proteomics assay, and higher HP1γ level is positively correlated with poorer outcomes in the clinic. Mechanistically, elevated HDAC1 in the bortezomib-resistant myeloma cells deacetylates HP1γ at lysine 5 and consequently alleviates the ubiquitin-mediated protein degradation, as well as the aberrant DNA repair capacity. HP1γ interacts with the MDC1 to induce DNA repair, and simultaneously the deacetylation modification and the interaction with MDC1 enhance the nuclear condensation of HP1γ protein and the chromatin accessibility of its target genes governing sensitivity to proteasome inhibitors, such as CD40, FOS and JUN. Thus, targeting HP1γ stability by using HDAC1 inhibitor re-sensitizes bortezomib-resistant myeloma cells to proteasome inhibitors treatment in vitro and in vivo. Our findings elucidate a previously unrecognized role of HP1γ in inducing drug resistance to proteasome inhibitors of myeloma cells and suggest that targeting HP1γ may be efficacious for overcoming drug resistance in refractory or relapsed multiple myeloma patients.
De novo lipogenesis fuels adipocyte autophagosome and lysosome membrane dynamics
Authors: Rowland Leslie A. , Guilherme Adilson , Henriques Felipe , DiMarzio Chloe , Munroe Sean , Wetoska Nicole , Kelly Mark , Reddig Keith , Hendricks Gregory , Pan Meixia , Han Xianlin , Ilkayeva Olga R. , Newgard Christopher B. , Czech Michael P.
Published: March 2023

Adipocytes robustly synthesize fatty acids (FA) from carbohydrate through the de novo lipogenesis (DNL) pathway, yet surprisingly DNL contributes little to their abundant triglyceride stored in lipid droplets. This conundrum raises the hypothesis that adipocyte DNL instead enables membrane expansions to occur in processes like autophagy, which requires an abundant supply of phospholipids. We report here that adipocyte Fasn deficiency in vitro and in vivo markedly impairs autophagy, evident by autophagosome accumulation and severely compromised degradation of the autophagic substrate p62. Our data indicate the impairment occurs at the level of autophagosome-lysosome fusion, and indeed, loss of Fasn decreases certain membrane phosphoinositides necessary for autophagosome and lysosome maturation and fusion. Autophagy dependence on FA produced by Fasn is not fully alleviated by exogenous FA in cultured adipocytes, and interestingly, imaging studies reveal that Fasn colocalizes with nascent autophagosomes. Together, our studies identify DNL as a critical source of FAs to fuel autophagosome and lysosome maturation and fusion in adipocytes.
PCR-like performance of rapid test with permselective tunable nanotrap
Authors: Park Seong Jun , Lee Seungmin , Lee Dongtak , Lee Na Eun , Park Jeong Soo , Hong Ji Hye , Jang Jae Won , Kim Hyunji , Roh Seokbeom , Lee Gyudo , Lee Dongho , Cho Sung-Yeon , Park Chulmin , Lee Dong-Gun , Lee Raeseok , Nho Dukhee , Yoon Dae Sung , Yoo Yong Kyoung , Lee Jeong Hoon
Published: March 2023

Highly sensitive rapid testing for COVID-19 is essential for minimizing virus transmission, especially before the onset of symptoms and in asymptomatic cases. Here, we report bioengineered enrichment tools for lateral flow assays (LFAs) with enhanced sensitivity and specificity (BEETLES2), achieving enrichment of SARS-CoV-2 viruses, nucleocapsid (N) proteins and immunoglobulin G (IgG) with 3-minute operation. The limit of detection is improved up to 20-fold. We apply this method to clinical samples, including 83% with either intermediate (35%) or low viral loads (48%), collected from 62 individuals (n = 42 for positive and n = 20 for healthy controls). We observe diagnostic sensitivity, specificity, and accuracy of 88.1%, 100%, and 91.9%, respectively, compared with commercial LFAs alone achieving 14.29%, 100%, and 41.94%, respectively. BEETLES2, with permselectivity and tunability, can enrich the SARS-CoV-2 virus, N proteins, and IgG in the nasopharyngeal/oropharyngeal swab, saliva, and blood serum, enabling reliable and sensitive point-of-care testing, facilitating fast early diagnosis.
Evolutionary differentiation of androgen receptor is responsible for sexual characteristic development in a teleost fish
Authors: Ogino Yukiko , Ansai Satoshi , Watanabe Eiji , Yasugi Masaki , Katayama Yukitoshi , Sakamoto Hirotaka , Okamoto Keigo , Okubo Kataaki , Yamamoto Yasuhiro , Hara Ikuyo , Yamazaki Touko , Kato Ai , Kamei Yasuhiro , Naruse Kiyoshi , Ohta Kohei , Ogino Hajime , Sakamoto Tatsuya , Miyagawa Shinichi , Sato Tomomi , Yamada Gen , Baker Michael E. , Iguchi Taisen
Published: March 2023

Teleost fishes exhibit complex sexual characteristics in response to androgens, such as fin enlargement and courtship display. However, the molecular mechanisms underlying their evolutionary acquisition remain largely unknown. To address this question, we analyse medaka (Oryzias latipes) mutants deficient in teleost-specific androgen receptor ohnologs (ara and arb). We discovered that neither ar ohnolog was required for spermatogenesis, whilst they appear to be functionally redundant for the courtship display in males. However, both were required for reproductive success: ara for tooth enlargement and the reproductive behaviour eliciting female receptivity, arb for male-specific fin morphogenesis and sexual motivation. We further showed that differences between the two ar ohnologs in their transcription, cellular localisation of their encoded proteins, and their downstream genetic programmes could be responsible for the phenotypic diversity between the ara and arb mutants. These findings suggest that the ar ohnologs have diverged in two ways: first, through the loss of their roles in spermatogenesis and second, through gene duplication followed by functional differentiation that has likely resolved the pleiotropic roles derived from their ancestral gene. Thus, our results provide insights into how genome duplication impacts the massive diversification of sexual characteristics in the teleost lineage.
Nanoarchitecture factors of solid electrolyte interphase formation via 3D nano-rheology microscopy and surface force-distance spectroscopy
Authors: Chen Yue , Wu Wenkai , Gonzalez-Munoz Sergio , Forcieri Leonardo , Wells Charlie , Jarvis Samuel P. , Wu Fangling , Young Robert , Dey Avishek , Isaacs Mark , Nagarathinam Mangayarkarasi , Palgrave Robert G. , Tapia-Ruiz Nuria , Kolosov Oleg V.
Published: March 2023

The solid electrolyte interphase in rechargeable Li-ion batteries, its dynamics and, significantly, its nanoscale structure and composition, hold clues to high-performing and safe energy storage. Unfortunately, knowledge of solid electrolyte interphase formation is limited due to the lack of in situ nano-characterization tools for probing solid-liquid interfaces. Here, we link electrochemical atomic force microscopy, three-dimensional nano-rheology microscopy and surface force-distance spectroscopy, to study, in situ and operando, the dynamic formation of the solid electrolyte interphase starting from a few 0.1 nm thick electrical double layer to the full three-dimensional nanostructured solid electrolyte interphase on the typical graphite basal and edge planes in a Li-ion battery negative electrode. By probing the arrangement of solvent molecules and ions within the electric double layer and quantifying the three-dimensional mechanical property distribution of organic and inorganic components in the as-formed solid electrolyte interphase layer, we reveal the nanoarchitecture factors and atomistic picture of initial solid electrolyte interphase formation on graphite-based negative electrodes in strongly and weakly solvating electrolytes.
DNA-dependent protein kinase catalytic subunit (DNA-PKcs) drives chronic kidney disease progression in male mice
Authors: Yang Yunwen , Liu Suwen , Wang Peipei , Ouyang Jing , Zhou Ning , Zhang Yue , Huang Songming , Jia Zhanjun , Zhang Aihua
Published: March 2023

Kidney injury initiates epithelial dedifferentiation and myofibroblast activation during the progression of chronic kidney disease. Herein, we find that the expression of DNA-PKcs is significantly increased in the kidney tissues of both chronic kidney disease patients and male mice induced by unilateral ureteral obstruction and unilateral ischemia-reperfusion injury. In vivo, knockout of DNA-PKcs or treatment with its specific inhibitor NU7441 hampers the development of chronic kidney disease in male mice. In vitro, DNA-PKcs deficiency preserves epithelial cell phenotype and inhibits fibroblast activation induced by transforming growth factor-beta 1. Additionally, our results show that TAF7, as a possible substrate of DNA-PKcs, enhances mTORC1 activation by upregulating RAPTOR expression, which subsequently promotes metabolic reprogramming in injured epithelial cells and myofibroblasts. Taken together, DNA-PKcs can be inhibited to correct metabolic reprogramming via the TAF7/mTORC1 signaling in chronic kidney disease, and serve as a potential target for treating chronic kidney disease.
Aggregation pheromones have a non-linear effect on oviposition behavior in Drosophila melanogaster
Authors: Verschut Thomas A. , Ng Renny , Doubovetzky Nicolas P. , Le Calvez Guillaume , Sneep Jan L. , Minnaard Adriaan J. , Su Chih-Ying , Carlsson Mikael A. , Wertheim Bregje , Billeter Jean-Christophe
Published: March 2023

Female fruit flies (Drosophila melanogaster) oviposit at communal sites where the larvae may cooperate or compete for resources depending on group size. This offers a model system to determine how females assess quantitative social information. We show that the concentration of pheromones found on a substrate increases linearly with the number of adult flies that have visited that site. Females prefer oviposition sites with pheromone concentrations corresponding to an intermediate number of previous visitors, whereas sites with low or high concentrations are unattractive. This dose-dependent decision is based on a blend of 11-cis-Vaccenyl Acetate (cVA) indicating the number of previous visitors and heptanal (a novel pheromone deriving from the oxidation of 7-Tricosene), which acts as a dose-independent co-factor. This response is mediated by detection of cVA by odorant receptor neurons Or67d and Or65a, and at least five different odorant receptor neurons for heptanal. Our results identify a mechanism allowing individuals to transform a linear increase of pheromones into a non-linear behavioral response.
Rational design of heterogenized molecular phthalocyanine hybrid single-atom electrocatalyst towards two-electron oxygen reduction
Authors: Fan Wenjun , Duan Zhiyao , Liu Wei , Mehmood Rashid , Qu Jiating , Cao Yucheng , Guo Xiangyang , Zhong Jun , Zhang Fuxiang
Published: March 2023

Single-atom catalysts supported on solid substrates have inspired extensive interest, but the rational design of high-efficiency single-atom catalysts is still plagued by ambiguous structure determination of active sites and its local support effect. Here, we report hybrid single-atom catalysts by an axial coordination linkage of molecular cobalt phthalocyanine with carbon nanotubes for selective oxygen reduction reaction by screening from a series of metal phthalocyanines via preferential density-functional theory calculations. Different from conventional heterogeneous single-atom catalysts, the hybrid single-atom catalysts are proven to facilitate rational screening of target catalysts as well as understanding of its underlying oxygen reduction reaction mechanism due to its well-defined active site structure and clear coordination linkage in the hybrid single-atom catalysts. Consequently, the optimized Co hybrid single-atom catalysts exhibit improved 2e− oxygen reduction reaction performance compared to the corresponding homogeneous molecular catalyst in terms of activity and selectivity. When prepared as an air cathode in an air-breathing flow cell device, the optimized hybrid catalysts enable the oxygen reduction reaction at 300 mA cm−2 exhibiting a stable Faradaic efficiency exceeding 90% for 25 h.
Structural conservation of HBV-like capsid proteins over hundreds of millions of years despite the shift from non-enveloped to enveloped life-style
Authors: Pfister Sara , Rabl Julius , Wiegand Thomas , Mattei Simone , Malär Alexander A. , Lecoq Lauriane , Seitz Stefan , Bartenschlager Ralf , Böckmann Anja , Nassal Michael , Boehringer Daniel , Meier Beat H.
Published: March 2023

The discovery of nackednaviruses provided new insight into the evolutionary history of the hepatitis B virus (HBV): The common ancestor of HBV and nackednaviruses was non-enveloped and while HBV acquired an envelope during evolution, nackednaviruses remained non-enveloped. We report the capsid structure of the African cichlid nackednavirus (ACNDV), determined by cryo-EM at 3.7 Å resolution. This enables direct comparison with the known capsid structures of HBV and duck HBV, prototypic representatives of the mammalian and avian lineages of the enveloped Hepadnaviridae, respectively. The sequence identity with HBV is 24% and both the ACNDV capsid protein fold and the capsid architecture are very similar to those of the Hepadnaviridae and HBV in particular. Acquisition of the hepadnaviral envelope was thus not accompanied by a major change in capsid structure. Dynamic residues at the spike tip are tentatively assigned by solid-state NMR, while the C-terminal domain is invisible due to dynamics. Solid-state NMR characterization of the capsid structure reveals few conformational differences between the quasi-equivalent subunits of the ACNDV capsid and an overall higher capsid structural disorder compared to HBV. Despite these differences, the capsids of ACNDV and HBV are structurally highly similar despite the 400 million years since their separation.
Affinity maturation generates pathogenic antibodies with dual reactivity to DNase1L3 and dsDNA in systemic lupus erythematosus
Authors: Gomez-Bañuelos Eduardo , Yu Yikai , Li Jessica , Cashman Kevin S. , Paz Merlin , Trejo-Zambrano Maria Isabel , Bugrovsky Regina , Wang Youliang , Chida Asiya Seema , Sherman-Baust Cheryl A. , Ferris Dylan P. , Goldman Daniel W. , Darrah Erika , Petri Michelle , Sanz Iñaki , Andrade Felipe
Published: March 2023

Anti-dsDNA antibodies are pathogenically heterogeneous, implying distinct origins and antigenic properties. Unexpectedly, during the clinical and molecular characterization of autoantibodies to the endonuclease DNase1L3 in patients with systemic lupus erythematosus (SLE), we identified a subset of neutralizing anti-DNase1L3 antibodies previously catalogued as anti-dsDNA. Based on their variable heavy-chain (VH) gene usage, these antibodies can be divided in two groups. One group is encoded by the inherently autoreactive VH4-34 gene segment, derives from anti-DNase1L3 germline-encoded precursors, and gains cross-reactivity to dsDNA – and some additionally to cardiolipin – following somatic hypermutation. The second group, originally defined as nephritogenic anti-dsDNA antibodies, is encoded by diverse VH gene segments. Although affinity maturation results in dual reactivity to DNase1L3 and dsDNA, their binding efficiencies favor DNase1L3 as the primary antigen. Clinical, transcriptional and monoclonal antibody data support that cross-reactive anti-DNase1L3/dsDNA antibodies are more pathogenic than single reactive anti-dsDNA antibodies. These findings point to DNase1L3 as the primary target of a subset of antibodies classified as anti-dsDNA, shedding light on the origin and pathogenic heterogeneity of antibodies reactive to dsDNA in SLE.
Sub-micron spin-based magnetic field imaging with an organic light emitting diode
Authors: Geng Rugang , Mena Adrian , Pappas William J. , McCamey Dane R.
Published: March 2023

Quantum sensing and imaging of magnetic fields has attracted broad interests due to its potential for high sensitivity and spatial resolution. Common systems used for quantum sensing require either optical excitation (e.g., nitrogen-vacancy centres in diamond, atomic vapor magnetometers), or cryogenic temperatures (e.g., SQUIDs, superconducting qubits), which pose challenges for chip-scale integration and commercial scalability. Here, we demonstrate an integrated organic light emitting diode (OLED) based solid-state sensor for magnetic field imaging, which employs spatially resolved magnetic resonance to provide a robust mapping of magnetic fields. By considering the monolithic OLED as an array of individual virtual sensors, we achieve sub-micron magnetic field mapping with field sensitivity of ~160 µT Hz−1/2 µm−2. Our work demonstrates a chip-scale OLED-based laser free magnetic field sensor and an approach to magnetic field mapping built on a commercially relevant and manufacturable technology.
Phosphoglycerate dehydrogenase activates PKM2 to phosphorylate histone H3T11 and attenuate cellular senescence
Authors: Wu Yinsheng , Tang Lixu , Huang Han , Yu Qi , Hu Bicheng , Wang Gang , Ge Feng , Yin Tailang , Li Shanshan , Yu Xilan
Published: March 2023

Vascular endothelial cells (ECs) senescence correlates with the increase of cardiovascular diseases in ageing population. Although ECs rely on glycolysis for energy production, little is known about the role of glycolysis in ECs senescence. Here, we report a critical role for glycolysis-derived serine biosynthesis in preventing ECs senescence. During senescence, the expression of serine biosynthetic enzyme PHGDH is significantly reduced due to decreased transcription of the activating transcription factor ATF4, which leads to reduction of intracellular serine. PHGDH prevents premature senescence primarily by enhancing the stability and activity of pyruvate kinase M2 (PKM2). Mechanistically, PHGDH interacts with PKM2, which prevents PCAF-catalyzed PKM2 K305 acetylation and subsequent degradation by autophagy. In addition, PHGDH facilitates p300-catalyzed PKM2 K433 acetylation, which promotes PKM2 nuclear translocation and stimulates its activity to phosphorylate H3T11 and regulate the transcription of senescence-associated genes. Vascular endothelium-targeted expression of PHGDH and PKM2 ameliorates ageing in mice. Our findings reveal that enhancing serine biosynthesis could become a therapy to promote healthy ageing.
Adipocyte YTH N(6)-methyladenosine RNA-binding protein 1 protects against obesity by promoting white adipose tissue beiging in male mice
Authors: Yan Sujun , Zhou Xiaoling , Wu Canlan , Gao Yunyi , Qian Yu , Hou Jingyu , Xie Renxiang , Han Bing , Chen Zhanghui , Wei Saisai , Gao Xiangwei
Published: March 2023

Obesity, one of the most serious public health issues, is caused by the imbalance of energy intake and energy expenditure. N(6)-methyladenosine (m6A) RNA modification has been recently identified as a key regulator of obesity, while the detailed mechanism is elusive. Here, we find that YTH RNA binding protein 1 (YTHDF1), an m6A reader, acts as an essential regulator of white adipose tissue metabolism. The expression of YTHDF1 decreases in adipose tissue of male mice fed a high-fat diet. Adipocyte-specific Ythdf1 deficiency exacerbates obesity-induced metabolic defects and inhibits beiging of inguinal white adipose tissue (iWAT) in male mice. By contrast, male mice with WAT-specific YTHDF1 overexpression are resistant to obesity and shows promotion of beiging. Mechanistically, YTHDF1 regulates the translation of diverse m6A-modified mRNAs. In particular, YTHDF1 facilitates the translation of bone morphogenetic protein 8b (Bmp8b) in an m6A-dependent manner to induce the beiging process. Here, we show that YTHDF1 may be an potential therapeutic target for the management of obesity-associated diseases.
An integrated photonic-assisted phased array transmitter for direct fiber to mm-wave links
Authors: Sanjari Pouria , Aflatouni Firooz
Published: March 2023

Millimeter-wave (mm-wave) phased arrays can realize multi-Gb/s communication links but face challenges such as signal distribution and higher power consumption hindering their widespread deployment. Hybrid photonic mm-wave solutions combined with fiber-optics can address some of these bottlenecks. Here, we report an integrated photonic-assisted phased array transmitter applicable for low-power, compact radio heads in fiber to mm-wave fronthaul links. The transmitter utilizes optical heterodyning within an electronically controlled photonic network for mm-wave generation, beamforming, and steering. A photonic matrix phase adjustment architecture reduces the number of phase-shift elements from M × N to M + N lowering area and power requirements. A proof-of-concept 2 × 8 phased array transmitter is implemented that can operate from 24–29 GHz, has a steering range of 40°, and achieves 5 dBm EIRP at an optical power of 55 mW without using active mm-wave electronics. Data streams at 2.5 Gb/s are transmitted over 3.6 km of optical fiber and wirelessly transmitted attaining bit-error rates better than 10−11.
The cellular and KSHV A-to-I RNA editome in primary effusion lymphoma and its role in the viral lifecycle
Authors: Rajendren Suba , Ye Xiang , Dunker William , Richardson Antiana , Karijolich John
Published: March 2023

Adenosine-to-inosine RNA editing is a major contributor to transcriptome diversity in animals with far-reaching biological consequences. Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiological agent of several human malignancies including primary effusion lymphoma (PEL). The extent of RNA editing within the KSHV transcriptome is unclear as is its contribution to the viral lifecycle. Here, we leverage a combination of biochemical and genomic approaches to determine the RNA editing landscape in host- and KSHV transcriptomes during both latent and lytic replication in PEL. Analysis of RNA editomes reveals it is dynamic, with increased editing upon reactivation and the potential to deregulate pathways critical for latency and tumorigenesis. In addition, we identify conserved RNA editing events within a viral microRNA and discover their role in miRNA biogenesis as well as viral infection. Together, these results describe the editome of PEL cells as well as a critical role for A-to-I editing in the KSHV lifecycle.
Insights into the formation and evolution of extraterrestrial amino acids from the asteroid Ryugu
Authors: Potiszil Christian , Ota Tsutomu , Yamanaka Masahiro , Sakaguchi Chie , Kobayashi Katsura , Tanaka Ryoji , Kunihiro Tak , Kitagawa Hiroshi , Abe Masanao , Miyazaki Akiko , Nakato Aiko , Nakazawa Satoru , Nishimura Masahiro , Okada Tatsuaki , Saiki Takanao , Tanaka Satoshi , Terui Fuyuto , Tsuda Yuichi , Usui Tomohiro , Watanabe Sei-ichiro , Yada Toru , Yogata Kasumi , Yoshikawa Makoto , Nakamura Eizo
Published: March 2023

All life on Earth contains amino acids and carbonaceous chondrite meteorites have been suggested as their source at the origin of life on Earth. While many meteoritic amino acids are considered indigenous, deciphering the extent of terrestrial contamination remains an issue. The Ryugu asteroid fragments (JAXA Hayabusa2 mission), represent the most uncontaminated primitive extraterrestrial material available. Here, the concentrations of amino acids from two particles from different touchdown sites (TD1 and TD2) are reported. The concentrations show that N,N-dimethylglycine (DMG) is the most abundant amino acid in the TD1 particle, but below detection limit in the other. The TD1 particle mineral components indicate it experienced more aqueous alteration. Furthermore, the relationships between the amino acids and the geochemistry suggest that DMG formed on the Ryugu progenitor body during aqueous alteration. The findings highlight the importance of aqueous chemistry for defining the ultimate concentrations of amino acids in primitive extraterrestrial samples.
Spatial transcriptomics using multiplexed deterministic barcoding in tissue
Authors: Wirth Johannes , Huber Nina , Yin Kelvin , Brood Sophie , Chang Simon , Martinez-Jimenez Celia P. , Meier Matthias
Published: March 2023

Spatially resolved transcriptomics of tissue sections enables advances in fundamental and applied biomedical research. Here, we present Multiplexed Deterministic Barcoding in Tissue (xDBiT) to acquire spatially resolved transcriptomes of nine tissue sections in parallel. New microfluidic chips were developed to spatially encode mRNAs over a total tissue area of 1.17 cm2 with a 50 µm resolution. Optimization of the biochemical protocol increased read and gene counts per spot by one order of magnitude compared to previous reports. Furthermore, the introduction of alignment markers allowed seamless registration of images and spatial transcriptomic spots. Together with technological advances, we provide an open-source computational pipeline to prepare raw sequencing data for downstream analysis. The functionality of xDBiT was demonstrated by acquiring 16 spatially resolved transcriptomic datasets from five different murine organs, including the cerebellum, liver, kidney, spleen, and heart. Factor analysis and deconvolution of spatial transcriptomes allowed for in-depth characterization of the murine kidney.
Multistability, intermittency, and hybrid transitions in social contagion models on hypergraphs
Authors: Ferraz de Arruda Guilherme , Petri Giovanni , Rodriguez Pablo Martin , Moreno Yamir
Published: March 2023

Although ubiquitous, interactions in groups of individuals are not yet thoroughly studied. Frequently, single groups are modeled as critical-mass dynamics, which is a widespread concept used not only by academics but also by politicians and the media. However, less explored questions are how a collection of groups will behave and how their intersection might change the dynamics. Here, we formulate this process as binary-state dynamics on hypergraphs. We showed that our model has a rich behavior beyond discontinuous transitions. Notably, we have multistability and intermittency. We demonstrated that this phenomenology could be associated with community structures, where we might have multistability or intermittency by controlling the number or size of bridges between communities. Furthermore, we provided evidence that the observed transitions are hybrid. Our findings open new paths for research, ranging from physics, on the formal calculation of quantities of interest, to social sciences, where new experiments can be designed.