bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling the Dynamics of Supraglacial Rivers and Distributed Meltwater Flow With the Subaerial Drainage System (SaDS) Model
Authors: Hill Tim , Dow Christine F.
Published: November 2021

Meltwater produced at the surface of glaciers and ice sheets has important implications for basal sliding rates and therefore ice flow velocities. In order to determine the role of supraglacial water in ice dynamics and predict future changes, we first need to understand and be able to accurately predict moulin input rates. To this end, we present the Subaerial Drainage System (SaDS) model. SaDS is a dynamic model that couples supraglacial runoff in the bare‐ice ablation zone in a distributed sheet with flow in discrete channels. Flow in the distributed sheet drives melt through potential energy dissipation, allowing a channel network to form naturally with no prior assumptions about channel locations. We apply the model to a synthetic ice sheet margin and carry out a suite of sensitivity tests. Modeled moulin inputs show expected behaviors including large diurnal variability, multi‐hour lags following peak surface melt, and demonstrate complex and diverse seasonal dynamics. The sensitivity tests illustrate the range of possible model behaviors and constrain the parameter values for which the model predicts physically realistic moulin inputs. We also apply the model to a ∼20 × 27 km2 catchment on the southwestern Greenland Ice Sheet using RACMO melt forcing and previously mapped moulin locations. Modeled supraglacial lake and stream locations match those mapped from Landsat 8 images, and moulin inputs show varied daily and seasonal dynamics. These results demonstrate that the model is a promising tool to provide moulin inputs for subglacial and ice dynamic studies.
Safety and efficacy of thalidomide in patients with transfusion-dependent β-thalassemia: a randomized clinical trial
Authors: Chen Jiang-Ming , Zhu Wei-Jian , Liu Jie , Wang Gui-Zhen , Chen Xiao-Qin , Tan Yun , Xu Wei-Wei , Qu Li-Wei , Li Jin-Yan , Yang Huan-Ju , Huang Lan , Cai Ning , Wang Wei-Da , Huang Ken , Xu Jian-Quan , Li Guo-Hui , He Sheng , Luo Tian-Ying , Huang Yi , Liu Song-Hua , Wu Wen-Qiang , Lu Qi-Yang , Zhou Mei-Guang , Chen Shu-Ying , Li Rong-Lan , Hu Mei-Ling , Huang Ying , Wei Jin-Hua , Li Jun-Min , Chen Sai-Juan , Zhou Guang-Biao
Published: November 2021

Thalidomide induces γ-globin expression in erythroid progenitor cells, but its efficacy on patients with transfusion-dependent β-thalassemia (TDT) remains unclear. In this phase 2, multi-center, randomized, double-blind clinical trial, we aimed to determine the safety and efficacy of thalidomide in TDT patients. A hundred patients of 14 years or older were randomly assigned to receive placebo or thalidomide for 12 weeks, followed by an extension phase of at least 36 weeks. The primary endpoint was the change of hemoglobin (Hb) level in the patients. The secondary endpoints included the red blood cell (RBC) units transfused and adverse effects. In the placebo-controlled period, Hb concentrations in patients treated with thalidomide achieved a median elevation of 14.0 (range, 2.5 to 37.5) g/L, whereas Hb in patients treated with placebo did not significantly change. Within the 12 weeks, the mean RBC transfusion volume for patients treated with thalidomide and placebo was 5.4 ± 5.0 U and 10.3 ± 6.4 U, respectively (P < 0.001). Adverse events of drowsiness, dizziness, fatigue, pyrexia, sore throat, and rash were more common with thalidomide than placebo. In the extension phase, treatment with thalidomide for 24 weeks resulted in a sustainable increase in Hb concentrations which reached 104.9 ± 19.0 g/L, without blood transfusion. Significant increase in Hb concentration and reduction in RBC transfusions were associated with non β0/β0 and HBS1L-MYB (rs9399137 C/T, C/C; rs4895441 A/G, G/G) genotypes. These results demonstrated that thalidomide is effective in patients with TDT.
The Physalis floridana genome provides insights into the biochemical and morphological evolution of Physalis fruits
Authors: Lu Jiangjie , Luo Meifang , Wang Li , Li Kunpeng , Yu Yongyi , Yang Weifei , Gong Pichang , Gao Huihui , Li Qiaoru , Zhao Jing , Wu Lanfeng , Zhang Mingshu , Liu Xueyang , Zhang Xuemei , Zhang Xian , Kang Jieyu , Yu Tongyuan , Li Zhimin , Jiao Yuannian , Wang Huizhong , He Chaoying
Published: November 2021

The fruits of Physalis (Solanaceae) have a unique structure, a lantern-like fruiting calyx known as inflated calyx syndrome (ICS) or the Chinese lantern, and are rich in steroid-related compounds. However, the genetic variations underlying the origin of these characteristic traits and diversity in Physalis remain largely unknown. Here, we present a high-quality chromosome-level reference genome assembly of Physalis floridana (~1.40 Gb in size) with a contig N50 of ~4.87 Mb. Through evolutionary genomics and experimental approaches, we found that the loss of the SEP-like MADS-box gene MBP21 subclade is likely a key mutation that, together with the previously revealed mutation affecting floral MPF2 expression, might have contributed to the origination of ICS in Physaleae, suggesting that the origination of a morphological novelty may have resulted from an evolutionary scenario in which one mutation compensated for another deleterious mutation. Moreover, the significant expansion of squalene epoxidase genes is potentially associated with the natural variation of steroid-related compounds in Physalis fruits. The results reveal the importance of gene gains (duplication) and/or subsequent losses as genetic bases of the evolution of distinct fruit traits, and the data serve as a valuable resource for the evolutionary genetics and breeding of solanaceous crops.
An infant case of pseudohypoaldosteronism type1A caused by a novel NR3C2 variant
Authors: Noda Saki , Aoyama Kohei , Kondo Yuto , Okamura Jun , Suzuki Atsushi , Yamaguchi Naoya , Yoshida Aya , Miyake Yoshishige
Published: November 2021

Pseudohypoaldosteronism type1A (PHA1A) is the renal form of pseudohypoaldosteronism with autosomal dominant inheritance. PHA1A is caused by haploinsufficiency of the mineralocorticoid receptor, which is encoded by NR3C2. We encountered an infant who was diagnosed with PHA1A due to hyponatremia, hyperkalemia, and poor weight gain in the neonatal period. She carried a novel heterozygous mutation (NM_000901.5: c.1757 + 1 G > C) in the splice donor site of IVS-2 in NR3C2.
Orbital torque in magnetic bilayers
Authors: Lee Dongjoon , Go Dongwook , Park Hyeon-Jong , Jeong Wonmin , Ko Hye-Won , Yun Deokhyun , Jo Daegeun , Lee Soogil , Go Gyungchoon , Oh Jung Hyun , Kim Kab-Jin , Park Byong-Guk , Min Byoung-Chul , Koo Hyun Cheol , Lee Hyun-Woo , Lee OukJae , Lee Kyung-Jin
Published: November 2021

The orbital Hall effect describes the generation of the orbital current flowing in a perpendicular direction to an external electric field, analogous to the spin Hall effect. As the orbital current carries the angular momentum as the spin current does, injection of the orbital current into a ferromagnet can result in torque on the magnetization, which provides a way to detect the orbital Hall effect. With this motivation, we examine the current-induced spin-orbit torques in various ferromagnet/heavy metal bilayers by theory and experiment. Analysis of the magnetic torque reveals the presence of the contribution from the orbital Hall effect in the heavy metal, which competes with the contribution from the spin Hall effect. In particular, we find that the net torque in Ni/Ta bilayers is opposite in sign to the spin Hall theory prediction but instead consistent with the orbital Hall theory, which unambiguously confirms the orbital torque generated by the orbital Hall effect. Our finding opens a possibility of utilizing the orbital current for spintronic device applications, and it will invigorate researches on spin-orbit-coupled phenomena based on orbital engineering.
Model-based assessment of Chikungunya and O’nyong-nyong virus circulation in Mali in a serological cross-reactivity context
Authors: Hozé Nathanaël , Diarra Issa , Sangaré Abdoul Karim , Pastorino Boris , Pezzi Laura , Kouriba Bourèma , Sagara Issaka , Dabo Abdoulaye , Djimdé Abdoulaye , Thera Mahamadou Ali , Doumbo Ogobara K. , de Lamballerie Xavier , Cauchemez Simon
Published: November 2021

Serological surveys are essential to quantify immunity in a population but serological cross-reactivity often impairs estimates of the seroprevalence. Here, we show that modeling helps addressing this key challenge by considering the important cross-reactivity between Chikungunya (CHIKV) and O’nyong-nyong virus (ONNV) as a case study. We develop a statistical model to assess the epidemiology of these viruses in Mali. We additionally calibrate the model with paired virus neutralization titers in the French West Indies, a region with known CHIKV circulation but no ONNV. In Mali, the model estimate of ONNV and CHIKV prevalence is 30% and 13%, respectively, versus 27% and 2% in non-adjusted estimates. While a CHIKV infection induces an ONNV response in 80% of cases, an ONNV infection leads to a cross-reactive CHIKV response in only 22% of cases. Our study shows the importance of conducting serological assays on multiple cross-reactive pathogens to estimate levels of virus circulation.
Multispecies and individual gas molecule detection using Stokes solitons in a graphene over-modal microresonator
Authors: Tan Teng , Yuan Zhongye , Zhang Hao , Yan Guofeng , Zhou Siyu , An Ning , Peng Bo , Soavi Giancarlo , Rao Yunjiang , Yao Baicheng
Published: November 2021

Soliton frequency combs generate equally-distant frequencies, offering a powerful tool for fast and accurate measurements over broad spectral ranges. The generation of solitons in microresonators can further improve the compactness of comb sources. However the geometry and the material’s inertness of pristine microresonators limit their potential in applications such as gas molecule detection. Here, we realize a two-dimensional-material functionalized microcomb sensor by asymmetrically depositing graphene in an over-modal microsphere. By using one single pump, spectrally trapped Stokes solitons belonging to distinct transverse mode families are co-generated in one single device. Such Stokes solitons with locked repetition rate but different offsets produce ultrasensitive beat notes in the electrical domain, offering unique advantages for selective and individual gas molecule detection. Moreover, the stable nature of the solitons enables us to trace the frequency shift of the dual-soliton beat-note with uncertainty <0.2 Hz and to achieve real-time individual gas molecule detection in vacuum, via an optoelectronic heterodyne detection scheme. This combination of atomically thin materials and microcombs shows the potential for compact photonic sensing with high performances and offers insights toward the design of versatile functionalized microcavity photonic devices.
Ecdysone regulates Drosophila wing disc size via a TORC1 dependent mechanism
Authors: Strassburger Katrin , Lutz Marilena , Müller Sandra , Teleman Aurelio A.
Published: November 2021

Most cells in a developing organ stop proliferating when the organ reaches a correct, final size. The underlying molecular mechanisms are not understood. We find that in Drosophila the hormone ecdysone controls wing disc size. To study how ecdysone affects wing size, we inhibit endogenous ecdysone synthesis and feed larvae exogenous ecdysone in a dose-controlled manner. For any given ecdysone dose, discs stop proliferating at a particular size, with higher doses enabling discs to reach larger sizes. Termination of proliferation coincides with a drop in TORC1, but not Dpp or Yki signaling. Reactivating TORC1 bypasses the termination of proliferation, indicating that TORC1 is a main downstream effector causing proliferation termination at the maximal ecdysone-dependent size. Experimental manipulation of Dpp or Yki signaling can bypass proliferation termination in hinge and notum regions, but not the pouch, suggesting that the mechanisms regulating proliferation termination may be distinct in different disc regions.
Mapping propagation of collective modes in Bi2Se3 and Bi2Te2.2Se0.8 topological insulators by near-field terahertz nanoscopy
Authors: Pogna Eva Arianna Aurelia , Viti Leonardo , Politano Antonio , Brambilla Massimo , Scamarcio Gaetano , Vitiello Miriam Serena
Published: November 2021

Near-field microscopy discloses a peculiar potential to explore novel quantum state of matter at the nanoscale, providing an intriguing playground to investigate, locally, carrier dynamics or propagation of photoexcited modes as plasmons, phonons, plasmon-polaritons or phonon-polaritons. Here, we exploit a combination of hyperspectral time domain spectroscopy nano-imaging and detectorless scattering near-field optical microscopy, at multiple terahertz frequencies, to explore the rich physics of layered topological insulators as Bi2Se3 and Bi2Te2.2Se0.8, hyperbolic materials with topologically protected surface states. By mapping the near-field scattering signal from a set of thin flakes of Bi2Se3 and Bi2Te2.2Se0.8 of various thicknesses, we shed light on the nature of the collective modes dominating their optical response in the 2-3 THz range. We capture snapshots of the activation of transverse and longitudinal optical phonons and reveal the propagation of sub-diffractional hyperbolic phonon-polariton modes influenced by the Dirac plasmons arising from the topological surface states and of bulk plasmons, prospecting new research directions in plasmonics, tailored nanophotonics, spintronics and quantum technologies.
Overactivated transport in the localized phase of the superconductor-insulator transition
Authors: Humbert V. , Ortuño M. , Somoza A. M. , Bergé L. , Dumoulin L. , Marrache-Kikuchi C. A.
Published: November 2021

Beyond a critical disorder, two-dimensional (2D) superconductors become insulating. In this Superconductor-Insulator Transition (SIT), the nature of the insulator is still controversial. Here, we present an extensive experimental study on insulating NbxSi1−x close to the SIT, as well as corresponding numerical simulations of the electrical conductivity. At low temperatures, we show that electronic transport is activated and dominated by charging energies. The sample thickness variation results in a large spread of activation temperatures, fine-tuned via disorder. We show numerically and experimentally that this originates from the localization length varying exponentially with thickness. At the lowest temperatures, there is an increase in activation energy related to the temperature at which this overactivated regime is observed. This relation, observed in many 2D systems shows that conduction is dominated by single charges that have to overcome the gap when entering superconducting grains.
Proteogenomic discovery of neoantigens facilitates personalized multi-antigen targeted T cell immunotherapy for brain tumors
Authors: Rivero-Hinojosa Samuel , Grant Melanie , Panigrahi Aswini , Zhang Huizhen , Caisova Veronika , Bollard Catherine M. , Rood Brian R.
Published: November 2021

Neoantigen discovery in pediatric brain tumors is hampered by their low mutational burden and scant tissue availability. Here we develop a proteogenomic approach combining tumor DNA/RNA sequencing and mass spectrometry proteomics to identify tumor-restricted (neoantigen) peptides arising from multiple genomic aberrations to generate a highly target-specific, autologous, personalized T cell immunotherapy. Our data indicate that aberrant splice junctions are the primary source of neoantigens in medulloblastoma, a common pediatric brain tumor. Proteogenomically identified tumor-specific peptides are immunogenic and generate MHC II-based T cell responses. Moreover, polyclonal and polyfunctional T cells specific for tumor-specific peptides effectively eliminate tumor cells in vitro. Targeting tumor-specific antigens obviates the issue of central immune tolerance while potentially providing a safety margin favoring combination with other immune-activating therapies. These findings demonstrate the proteogenomic discovery of immunogenic tumor-specific peptides and lay the groundwork for personalized targeted T cell therapies for children with brain tumors.
Accurate and scalable variant calling from single cell DNA sequencing data with ProSolo
Authors: Lähnemann David , Köster Johannes , Fischer Ute , Borkhardt Arndt , McHardy Alice C. , Schönhuth Alexander
Published: November 2021

Accurate single cell mutational profiles can reveal genomic cell-to-cell heterogeneity. However, sequencing libraries suitable for genotyping require whole genome amplification, which introduces allelic bias and copy errors. The resulting data violates assumptions of variant callers developed for bulk sequencing. Thus, only dedicated models accounting for amplification bias and errors can provide accurate calls. We present ProSolo for calling single nucleotide variants from multiple displacement amplified (MDA) single cell DNA sequencing data. ProSolo probabilistically models a single cell jointly with a bulk sequencing sample and integrates all relevant MDA biases in a site-specific and scalable—because computationally efficient—manner. This achieves a higher accuracy in calling and genotyping single nucleotide variants in single cells in comparison to state-of-the-art tools and supports imputation of insufficiently covered genotypes, when downstream tools cannot handle missing data. Moreover, ProSolo implements the first approach to control the false discovery rate reliably and flexibly. ProSolo is implemented in an extendable framework, with code and usage at: https://github.com/prosolo/prosolo
Mechanochemical synthesis of magnesium-based carbon nucleophiles in air and their use in organic synthesis
Authors: Takahashi Rina , Hu Anqi , Gao Pan , Gao Yunpeng , Pang Yadong , Seo Tamae , Jiang Julong , Maeda Satoshi , Takaya Hikaru , Kubota Koji , Ito Hajime
Published: November 2021

Since the discovery of Grignard reagents in 1900, the nucleophilic addition of magnesium-based carbon nucleophiles to various electrophiles has become one of the most powerful, versatile, and well-established methods for the formation of carbon−carbon bonds in organic synthesis. Grignard reagents are typically prepared via reactions between organic halides and magnesium metal in a solvent. However, this method usually requires the use of dry organic solvents, long reaction times, strict control of the reaction temperature, and inert-gas-line techniques. Despite the utility of Grignard reagents, these requirements still represent major drawbacks from both an environmental and an economic perspective, and often cause reproducibility problems. Here, we report the general mechanochemical synthesis of magnesium-based carbon nucleophiles (Grignard reagents in paste form) in air using a ball milling technique. These nucleophiles can be used directly for one-pot nucleophilic addition reactions with various electrophiles and nickel-catalyzed cross-coupling reactions under solvent-free conditions.
ABHD5 inhibits YAP-induced c-Met overexpression and colon cancer cell stemness via suppressing YAP methylation
Authors: Gu Yan , Chen Yanrong , Wei Lai , Wu Shuang , Shen Kaicheng , Liu Chengxiang , Dong Yan , Zhao Yang , Zhang Yue , Zhang Chi , Zheng Wenling , He Jiangyi , Wang Yunlong , Li Yifei , Zhao Xiaoxin , Wang Hongwei , Tan Jun , Wang Liting , Zhou Qi , Xie Ganfeng , Liang Houjie , Ou Juanjuan
Published: November 2021

Cancer stemness represents a major source of development and progression of colorectal cancer (CRC). c-Met critically contributes to CRC stemness, but how c-Met is activated in CRC remains elusive. We previously identified the lipolytic factor ABHD5 as an important tumour suppressor gene in CRC. Here, we show that loss of ABHD5 promotes c-Met activation to sustain CRC stemness in a non-canonical manner. Mechanistically, we demonstrate that ABHD5 interacts in the cytoplasm with the core subunit of the SET1A methyltransferase complex, DPY30, thereby inhibiting the nuclear translocation of DPY30 and activity of SET1A. In the absence of ABHD5, DPY30 translocates to the nucleus and supports SET1A-mediated methylation of YAP and histone H3, which sequesters YAP in the nucleus and increases chromatin accessibility to synergistically promote YAP-induced transcription of c-Met, thus promoting the stemness of CRC cells. This study reveals a novel role of ABHD5 in regulating histone/non-histone methylation and CRC stemness.
Repeated exposure with short-term behavioral stress resolves pre-existing stress-induced depressive-like behavior in mice
Authors: Lee Eun-Hwa , Park Jin-Young , Kwon Hye-Jin , Han Pyung-Lim
Published: November 2021

Chronic stress induces adaptive changes in the brain via the cumulative action of glucocorticoids, which is associated with mood disorders. Here we show that repeated daily five-minute restraint resolves pre-existing stress-induced depressive-like behavior in mice. Repeated injection of glucocorticoids in low doses mimics the anti-depressive effects of short-term stress. Repeated exposure to short-term stress and injection of glucocorticoids activate neurons in largely overlapping regions of the brain, as shown by c-Fos staining, and reverse distinct stress-induced gene expression profiles. Chemogenetic inhibition of neurons in the prelimbic cortex projecting to the nucleus accumbens, basolateral amygdala, or bed nucleus of the stria terminalis results in anti-depressive effects similarly to short-term stress exposure, while only inhibition of neurons in the prelimbic cortex projecting to the bed nucleus of the stria terminalis rescues defective glucocorticoid release. In summary, we show that short-term stress can reverse adaptively altered stress gains and resolve stress-induced depressive-like behavior.
A model of tension-induced fiber growth predicts white matter organization during brain folding
Authors: Garcia Kara E. , Wang Xiaojie , Kroenke Christopher D.
Published: November 2021

The past decade has experienced renewed interest in the physical processes that fold the developing cerebral cortex. Biomechanical models and experiments suggest that growth of the cortex, outpacing growth of underlying subcortical tissue (prospective white matter), is sufficient to induce folding. However, current models do not explain the well-established links between white matter organization and fold morphology, nor do they consider subcortical remodeling that occurs during the period of folding. Here we propose a framework by which cortical folding may induce subcortical fiber growth and organization. Simulations incorporating stress-induced fiber elongation indicate that subcortical stresses resulting from folding are sufficient to induce stereotyped fiber organization beneath gyri and sulci. Model predictions are supported by high-resolution ex vivo diffusion tensor imaging of the developing rhesus macaque brain. Together, results provide support for the theory of cortical growth-induced folding and indicate that mechanical feedback plays a significant role in brain connectivity.
Magnetization dependent tunneling conductance of ferromagnetic barriers
Authors: Wang Zhe , Gutiérrez-Lezama Ignacio , Dumcenco Dumitru , Ubrig Nicolas , Taniguchi Takashi , Watanabe Kenji , Giannini Enrico , Gibertini Marco , Morpurgo Alberto F.
Published: November 2021

Recent experiments on van der Waals antiferromagnets have shown that measuring the temperature (T) and magnetic field (H) dependence of the conductance allows their magnetic phase diagram to be mapped. Similarly, experiments on ferromagnetic CrBr3 barriers enabled the Curie temperature to be determined at H = 0, but a precise interpretation of the magnetoconductance data at H ≠ 0 is conceptually more complex, because at finite H there is no well-defined phase boundary. Here we perform systematic transport measurements on CrBr3 barriers and show that the tunneling magnetoconductance depends on H and T exclusively through the magnetization M(H, T) over the entire temperature range investigated. The phenomenon is reproduced by the spin-dependent Fowler–Nordheim model for tunneling, and is a direct manifestation of the spin splitting of the CrBr3 conduction band. Our analysis unveils a new approach to probe quantitatively different properties of atomically thin ferromagnetic insulators related to their magnetization by performing simple conductance measurements.
Immune cell topography predicts response to PD-1 blockade in cutaneous T cell lymphoma
Authors: Phillips Darci , Matusiak Magdalena , Gutierrez Belén Rivero , Bhate Salil S. , Barlow Graham L. , Jiang Sizun , Demeter Janos , Smythe Kimberly S. , Pierce Robert H. , Fling Steven P. , Ramchurren Nirasha , Cheever Martin A. , Goltsev Yury , West Robert B. , Khodadoust Michael S. , Kim Youn H. , Schürch Christian M. , Nolan Garry P.
Published: November 2021

Cutaneous T cell lymphomas (CTCL) are rare but aggressive cancers without effective treatments. While a subset of patients derive benefit from PD-1 blockade, there is a critically unmet need for predictive biomarkers of response. Herein, we perform CODEX multiplexed tissue imaging and RNA sequencing on 70 tumor regions from 14 advanced CTCL patients enrolled in a pembrolizumab clinical trial (NCT02243579). We find no differences in the frequencies of immune or tumor cells between responders and non-responders. Instead, we identify topographical differences between effector PD-1+ CD4+ T cells, tumor cells, and immunosuppressive Tregs, from which we derive a spatial biomarker, termed the SpatialScore, that correlates strongly with pembrolizumab response in CTCL. The SpatialScore coincides with differences in the functional immune state of the tumor microenvironment, T cell function, and tumor cell-specific chemokine recruitment and is validated using a simplified, clinically accessible tissue imaging platform. Collectively, these results provide a paradigm for investigating the spatial balance of effector and suppressive T cell activity and broadly leveraging this biomarker approach to inform the clinical use of immunotherapies.
Psychological stress impairs IL22-driven protective gut mucosal immunity against colonising pathobionts
Authors: Shaler Christopher R. , Parco Alexandra A. , Elhenawy Wael , Dourka Jasmeen , Jury Jennifer , Verdu Elena F. , Coombes Brian K.
Published: November 2021

Crohn’s disease is an inflammatory disease of the gastrointestinal tract characterized by an aberrant response to microbial and environmental triggers. This includes an altered microbiome dominated by Enterobacteriaceae and in particular adherent-invasive E. coli (AIEC). Clinical evidence implicates periods of psychological stress in Crohn’s disease exacerbation, and disturbances in the gut microbiome might contribute to the pathogenic mechanism. Here we show that stress-exposed mice develop ileal dysbiosis, dominated by the expansion of Enterobacteriaceae. In an AIEC colonisation model, stress-induced glucocorticoids promote apoptosis of CD45+CD90+ cells that normally produce IL-22, a cytokine that is essential for the maintenance of ileal mucosal barrier integrity. Blockade of glucocorticoid signaling or administration of recombinant IL-22 restores mucosal immunity, prevents ileal dysbiosis, and blocks AIEC expansion. We conclude that psychological stress impairs IL-22-driven protective immunity in the gut, which creates a favorable niche for the expansion of pathobionts that have been implicated in Crohn’s disease. Importantly, this work also shows that immunomodulation can counteract the negative effects of psychological stress on gut immunity and hence disease-associated dysbiosis.
Photoelectrocatalytic C–H halogenation over an oxygen vacancy-rich TiO2 photoanode
Authors: Li Zhenhua , Luo Lan , Li Min , Chen Wangsong , Liu Yuguang , Yang Jiangrong , Xu Si-Min , Zhou Hua , Ma Lina , Xu Ming , Kong Xianggui , Duan Haohong
Published: November 2021

Photoelectrochemical cells are emerging as powerful tools for organic synthesis. However, they have rarely been explored for C–H halogenation to produce organic halides of industrial and medicinal importance. Here we report a photoelectrocatalytic strategy for C–H halogenation using an oxygen-vacancy-rich TiO2 photoanode with NaX (X=Cl−, Br−, I−). Under illumination, the photogenerated holes in TiO2 oxidize the halide ions to corresponding radicals or X2, which then react with the substrates to yield organic halides. The PEC C–H halogenation strategy exhibits broad substrate scope, including arenes, heteroarenes, nonpolar cycloalkanes, and aliphatic hydrocarbons. Experimental and theoretical data reveal that the oxygen vacancy on TiO2 facilitates the photo-induced carriers separation efficiency and more importantly, promotes halide ions adsorption with intermediary strength and hence increases the activity. Moreover, we designed a self-powered PEC system and directly utilised seawater as both the electrolyte and chloride ions source, attaining chlorocyclohexane productivity of 412 µmol h−1 coupled with H2 productivity of 9.2 mL h−1, thus achieving a promising way to use solar for upcycling halogen in ocean resource into valuable organic halides.
Strong metal-support interactions induced by an ultrafast laser
Authors: Zhang Jian , Zhu Dezhi , Yan Jianfeng , Wang Chang-An
Published: November 2021

Supported metal catalysts play a crucial role in the modern industry. Constructing strong metal-support interactions (SMSI) is an effective means of regulating the interfacial properties of noble metal-based supported catalysts. Here, we propose a new strategy of ultrafast laser-induced SMSI that can be constructed on a CeO2-supported Pt system by confining electric field in localized interface. The nanoconfined field essentially boosts the formation of surface defects and metastable CeOx migration. The SMSI is evidenced by covering Pt nanoparticles with the CeOx thin overlayer and suppression of CO adsorption. The overlayer is permeable to the reactant molecules. Owing to the SMSI, the resulting Pt/CeO2 catalyst exhibits enhanced activity and stability for CO oxidation. This strategy of constructing SMSI can be extended not only to other noble metal systems (such as Au/TiO2, Pd/TiO2, and Pt/TiO2) but also on non-reducible oxide supports (such as Pt/Al2O3, Au/MgO, and Pt/SiO2), providing a universal way to engineer and develop high-performance supported noble metal catalysts.
Osseosurface electronics—thin, wireless, battery-free and multimodal musculoskeletal biointerfaces
Authors: Cai Le , Burton Alex , Gonzales David A. , Kasper Kevin Albert , Azami Amirhossein , Peralta Roberto , Johnson Megan , Bakall Jakob A. , Barron Villalobos Efren , Ross Ethan C. , Szivek John A. , Margolis David S. , Gutruf Philipp
Published: November 2021

Bioelectronic interfaces have been extensively investigated in recent years and advances in technology derived from these tools, such as soft and ultrathin sensors, now offer the opportunity to interface with parts of the body that were largely unexplored due to the lack of suitable tools. The musculoskeletal system is an understudied area where these new technologies can result in advanced capabilities. Bones as a sensor and stimulation location offer tremendous advantages for chronic biointerfaces because devices can be permanently bonded and provide stable optical, electromagnetic, and mechanical impedance over the course of years. Here we introduce a new class of wireless battery-free devices, named osseosurface electronics, which feature soft mechanics, ultra-thin form factor and miniaturized multimodal biointerfaces comprised of sensors and optoelectronics directly adhered to the surface of the bone. Potential of this fully implanted device class is demonstrated via real-time recording of bone strain, millikelvin resolution thermography and delivery of optical stimulation in freely-moving small animal models. Battery-free device architecture, direct growth to the bone via surface engineered calcium phosphate ceramic particles, demonstration of operation in deep tissue in large animal models and readout with a smartphone highlight suitable characteristics for exploratory research and utility as a diagnostic and therapeutic platform.
Direct observation of one-dimensional disordered diffusion channel in a chain-like thermoelectric with ultralow thermal conductivity
Authors: Zhang Jiawei , Roth Nikolaj , Tolborg Kasper , Takahashi Seiya , Song Lirong , Bondesgaard Martin , Nishibori Eiji , Iversen Bo B.
Published: November 2021

Structural disorder, highly effective in reducing thermal conductivity, is important in technological applications such as thermal barrier coatings and thermoelectrics. In particular, interstitial, disordered, diffusive atoms are common in complex crystal structures with ultralow thermal conductivity, but are rarely found in simple crystalline solids. Combining single-crystal synchrotron X-ray diffraction, the maximum entropy method, diffuse scattering, and theoretical calculations, here we report the direct observation of one-dimensional disordered In1+ chains in a simple chain-like thermoelectric InTe, which contains a significant In1+ vacancy along with interstitial indium sites. Intriguingly, the disordered In1+ chains undergo a static-dynamic transition with increasing temperature to form a one-dimensional diffusion channel, which is attributed to a low In1+-ion migration energy barrier along the c direction, a general feature in many other TlSe-type compounds. Our work provides a basis towards understanding ultralow thermal conductivity with weak temperature dependence in TlSe-type chain-like materials.
Micronutrient supplements can promote disruptive protozoan and fungal communities in the developing infant gut
Authors: Popovic Ana , Bourdon Celine , Wang Pauline W. , Guttman David S. , Soofi Sajid , Bhutta Zulfiqar A. , Bandsma Robert H. J. , Parkinson John , Pell Lisa G.
Published: November 2021

Supplementation with micronutrients, including vitamins, iron and zinc, is a key strategy to alleviate child malnutrition. However, association of gastrointestinal disorders with iron has led to ongoing debate over their administration. To better understand their impact on gut microbiota, we analyse the bacterial, protozoal, fungal and helminth communities of stool samples collected from a subset of 80 children at 12 and 24 months of age, previously enrolled into a large cluster randomized controlled trial of micronutrient supplementation in Pakistan (ClinicalTrials.gov identifier NCT00705445). We show that while bacterial diversity is reduced in supplemented children, vitamins and iron (as well as residence in a rural setting) may promote colonization with distinct protozoa and mucormycetes, whereas the addition of zinc appears to ameliorate this effect. We suggest that the risks and benefits of micronutrient interventions may depend on eukaryotic communities, potentially exacerbated by exposure to a rural setting. Larger studies are needed to evaluate the clinical significance of these findings and their impact on health outcomes.
Impact damping and vibration attenuation in nematic liquid crystal elastomers
Authors: Saed Mohand O. , Elmadih Waiel , Terentjev Andrew , Chronopoulos Dimitrios , Williamson David , Terentjev Eugene M.
Published: November 2021

Nematic liquid crystal elastomers (LCE) exhibit unique mechanical properties, placing them in a category distinct from other viscoelastic systems. One of their most celebrated properties is the ‘soft elasticity’, leading to a wide plateau of low, nearly-constant stress upon stretching, a characteristically slow stress relaxation, enhanced surface adhesion, and other remarkable effects. The dynamic soft response of LCE to shear deformations leads to the extremely large loss behaviour with the loss factor tanδ approaching unity over a wide temperature and frequency ranges, with clear implications for damping applications. Here we investigate this effect of anomalous damping, optimising the impact and vibration geometries to reach the greatest benefits in vibration isolation and impact damping by accessing internal shear deformation modes. We compare impact energy dissipation in shaped samples and projectiles, with elastic wave transmission and resonance, finding a good correlation between the results of such diverse tests. By comparing with ordinary elastomers used for industrial damping, we demonstrate that the nematic LCE is an exceptional damping material and propose directions that should be explored for further improvements in practical damping applications.
Machine learning of genomic features in organotropic metastases stratifies progression risk of primary tumors
Authors: Jiang Biaobin , Mu Quanhua , Qiu Fufang , Li Xuefeng , Xu Weiqi , Yu Jun , Fu Weilun , Cao Yong , Wang Jiguang
Published: November 2021

Metastatic cancer is associated with poor patient prognosis but its spatiotemporal behavior remains unpredictable at early stage. Here we develop MetaNet, a computational framework that integrates clinical and sequencing data from 32,176 primary and metastatic cancer cases, to assess metastatic risks of primary tumors. MetaNet achieves high accuracy in distinguishing the metastasis from the primary in breast and prostate cancers. From the prediction, we identify Metastasis-Featuring Primary (MFP) tumors, a subset of primary tumors with genomic features enriched in metastasis and demonstrate their higher metastatic risk and shorter disease-free survival. In addition, we identify genomic alterations associated with organ-specific metastases and employ them to stratify patients into various risk groups with propensities toward different metastatic organs. This organotropic stratification method achieves better prognostic value than the standard histological grading system in prostate cancer, especially in the identification of Bone-MFP and Liver-MFP subtypes, with potential in informing organ-specific examinations in follow-ups.
Bioorthogonal labeling of transmembrane proteins with non-canonical amino acids unveils masked epitopes in live neurons
Authors: Bessa-Neto Diogo , Beliu Gerti , Kuhlemann Alexander , Pecoraro Valeria , Doose Sören , Retailleau Natacha , Chevrier Nicolas , Perrais David , Sauer Markus , Choquet Daniel
Published: November 2021

Progress in biological imaging is intrinsically linked to advances in labeling methods. The explosion in the development of high-resolution and super-resolution imaging calls for new approaches to label targets with small probes. These should allow to faithfully report the localization of the target within the imaging resolution – typically nowadays a few nanometers - and allow access to any epitope of the target, in the native cellular and tissue environment. We report here the development of a complete labeling and imaging pipeline using genetic code expansion and non-canonical amino acids in neurons that allows to fluorescently label masked epitopes in target transmembrane proteins in live neurons, both in dissociated culture and organotypic brain slices. This allows us to image the differential localization of two AMPA receptor (AMPAR) auxiliary subunits of the transmembrane AMPAR regulatory protein family in complex with their partner with a variety of methods including widefield, confocal, and dSTORM super-resolution microscopy.
Single-cell analysis of diverse immune phenotypes in malignant pleural effusion
Authors: Huang Zhong-Yin , Shao Ming-Ming , Zhang Jian-Chu , Yi Feng-Shuang , Du Juan , Zhou Qiong , Wu Feng-Yao , Li Sha , Li Wei , Huang Xian-Zhen , Zhai Kan , Shi Huan-Zhong
Published: November 2021

The complex interactions among different immune cells have important functions in the development of malignant pleural effusion (MPE). Here we perform single-cell RNA sequencing on 62,382 cells from MPE patients induced by non-small cell lung cancer to describe the composition, lineage, and functional states of infiltrating immune cells in MPE. Immune cells in MPE display a number of transcriptional signatures enriched for regulatory T cells, B cells, macrophages, and dendritic cells compared to corresponding counterparts in blood. Helper T, cytotoxic T, regulatory T, and T follicular helper cells express multiple immune checkpoints or costimulatory molecules. Cell-cell interaction analysis identifies regulatory B cells with more interactions with CD4+ T cells compared to CD8+ T cells. Macrophages are transcriptionally heterogeneous and conform to M2 polarization characteristics. In addition, immune cells in MPE show the general up-regulation of glycolytic pathways associated with the hypoxic microenvironment. These findings show a detailed atlas of immune cells in human MPE and enhance the understanding of potential diagnostic and therapeutic targets in advanced non-small cell lung cancer.
Visual prototypes in the ventral stream are attuned to complexity and gaze behavior
Authors: Rose Olivia , Johnson James , Wang Binxu , Ponce Carlos R.
Published: November 2021

Early theories of efficient coding suggested the visual system could compress the world by learning to represent features where information was concentrated, such as contours. This view was validated by the discovery that neurons in posterior visual cortex respond to edges and curvature. Still, it remains unclear what other information-rich features are encoded by neurons in more anterior cortical regions (e.g., inferotemporal cortex). Here, we use a generative deep neural network to synthesize images guided by neuronal responses from across the visuocortical hierarchy, using floating microelectrode arrays in areas V1, V4 and inferotemporal cortex of two macaque monkeys. We hypothesize these images (“prototypes”) represent such predicted information-rich features. Prototypes vary across areas, show moderate complexity, and resemble salient visual attributes and semantic content of natural images, as indicated by the animals’ gaze behavior. This suggests the code for object recognition represents compressed features of behavioral relevance, an underexplored aspect of efficient coding.
Asymmetric construction of acyclic quaternary stereocenters via direct enantioselective additions of α-alkynyl ketones to allenamides
Authors: Wang Jiawen , He Faqian , Yang Xiaoyu
Published: November 2021

Acyclic quaternary stereocenters are widely present in a series of biologically active natural products and pharmaceuticals. However, development of highly efficient asymmetric catalytic methods for the construction of these privileged motifs represents a longstanding challenge in organic synthesis. Herein, an efficient chiral phosphoric acid catalyzed direct asymmetric addition of α-alkynyl acyclic ketones with allenamides has been developed, furnishing the acyclic all-carbon quaternary stereocenters with excellent regioselectivities and high enantioselectivities. Extensive and detailed experimental mechanistic studies were performed to investigate the mechanism of this reaction. Despite a novel covalent allyl phosphate intermediate was found in these reactions, further studies indicated that a SN2-type mechanism with the ketone nucleophiles is not very possible. Instead, a more plausible mechanism involving the elimination of the allyl phosphate to give the α,β-unsaturated iminium intermediate, which underwent the asymmetric conjugate addition with the enol form of ketone nucleophiles under chiral anion catalysis, was proposed. In virtue of the fruitful functional groups bearing in the chiral products, the diverse derivatizations of the chiral products provided access to a wide array of chiral scaffolds with quaternary stereocenters.
Inflammasome-mediated GSDMD activation facilitates escape of Candida albicans from macrophages
Authors: Ding Xionghui , Kambara Hiroto , Guo Rongxia , Kanneganti Apurva , Acosta-Zaldívar Maikel , Li Jiajia , Liu Fei , Bei Ting , Qi Wanjun , Xie Xuemei , Han Wenli , Liu Ningning , Zhang Cunling , Zhang Xiaoyu , Yu Hongbo , Zhao Li , Ma Fengxia , Köhler Julia R. , Luo Hongbo R.
Published: November 2021

Candida albicansis the most common cause of fungal sepsis. Inhibition of inflammasome activity confers resistance to polymicrobial and LPS-induced sepsis; however, inflammasome signaling appears to protect againstC. albicansinfection, so inflammasome inhibitors are not clinically useful for candidiasis. Here we show disruption of GSDMD, a known inflammasome target and key pyroptotic cell death mediator, paradoxically alleviates candidiasis, improving outcomes and survival ofCandida-infected mice. Mechanistically,C. albicanshijacked the canonical inflammasome-GSDMD axis-mediated pyroptosis to promote their escape from macrophages, deploying hyphae and candidalysin, a pore-forming toxin expressed by hyphae. GSDMD inhibition alleviated candidiasis by preventingC. albicansescape from macrophages while maintaining inflammasome-dependent but GSDMD-independent IL-1β production for anti-fungal host defenses. This study demonstrates key functions for GSDMD inCandida’s escape from host immunity in vitro and in vivo and suggests that GSDMD may be a potential therapeutic target inC. albicans-induced sepsis.
Evidence for anisotropic spin-triplet Andreev reflection at the 2D van der Waals ferromagnet/superconductor interface
Authors: Cai Ranran , Yao Yunyan , Lv Peng , Ma Yang , Xing Wenyu , Li Boning , Ji Yuan , Zhou Huibin , Shen Chenghao , Jia Shuang , Xie X. C. , Žutić Igor , Sun Qing-Feng , Han Wei
Published: November 2021

Fundamental symmetry breaking and relativistic spin–orbit coupling give rise to fascinating phenomena in quantum materials. Of particular interest are the interfaces between ferromagnets and common s-wave superconductors, where the emergent spin-orbit fields support elusive spin-triplet superconductivity, crucial for superconducting spintronics and topologically-protected Majorana bound states. Here, we report the observation of large magnetoresistances at the interface between a quasi-two-dimensional van der Waals ferromagnet Fe0.29TaS2 and a conventional s-wave superconductor NbN, which provides the possible experimental evidence for the spin-triplet Andreev reflection and induced spin-triplet superconductivity at ferromagnet/superconductor interface arising from Rashba spin-orbit coupling. The temperature, voltage, and interfacial barrier dependences of the magnetoresistance further support the induced spin-triplet superconductivity and spin-triplet Andreev reflection. This discovery, together with the impressive advances in two-dimensional van der Waals ferromagnets, opens an important opportunity to design and probe superconducting interfaces with exotic properties.
Pre-existing immunity and vaccine history determine hemagglutinin-specific CD4 T cell and IgG response following seasonal influenza vaccination
Authors: Wild Katharina , Smits Maike , Killmer Saskia , Strohmeier Shirin , Neumann-Haefelin Christoph , Bengsch Bertram , Krammer Florian , Schwemmle Martin , Hofmann Maike , Thimme Robert , Zoldan Katharina , Boettler Tobias
Published: November 2021

Effectiveness of seasonal influenza vaccination varies between individuals and might be affected by vaccination history among other factors. Here we show, by monitoring frequencies of CD4 T cells specific to the conserved hemagglutinin epitope HA118-132 and titres of IgG against the corresponding recombinant hemagglutinin protein, that antigen-specific CD4 T cell and antibody responses are closely linked to pre-existing immunity and vaccine history. Upon immunization, a strong early reaction is observed in all vaccine naïve participants and also in vaccine experienced individuals who have not received the respective seasonal vaccine in the previous year. This response is characterized by HA118-132 specific CD4 T cells with a follicular helper T cell phenotype and by ascending titers of hemagglutinin-specific antibodies from baseline to day 28 following vaccination. This trend was observed in only a proportion of those participants who received the seasonal vaccine the year preceding the study. Regardless of history, levels of pre-existing antibodies and CD127 expression on CD4 T cells at baseline were the strongest predictors of robust early response. Thus, both pre-existing immunity and vaccine history contribute to the response to seasonal influenza vaccines.