bluuebunny/crossref_metadata_2025 huggingface dataset:
Ionospheric Disturbances Observed From a Single GPS Station in Hong Kong During the Passage of Super Typhoon Hato in 2017
Authors: Yu Shiwei , Liu Zhizhao , Lee Tsz Cheung
Published: December 2021

The powerful convection in the lower atmosphere, for example, tropical cyclones (TCs), has a high probability of causing ionospheric disturbances. We observed evident ionospheric disturbances during the passage of Super Typhoon Hato in 2017 by analyzing the highest elevation vertical total electron content (HeVTEC) time series, that is, the VTEC from the Global Positioning System (GPS) satellite with the highest elevation at each epoch, retrieved from a single GPS station in Hong Kong. The results demonstrate that the daily maximum of HeVTEC time series on each day during the TC period experienced a large fluctuation ranging from 33.5 TEC unit (TECU) to the peak value 62.0 TECU. The peak value 62.0 TECU occurred on the TC landfall day 23 August 2017, approximately twice as high as that of non‐TC‐impacted days. We also found that the TEC spatial gradients above the landfall area increased by around 50% and 200% in the north‐to‐south and west‐to‐east directions, respectively. We also examined the daily mean bias (MB) of VTEC above Hong Kong with respect to the mean VTEC during the past 27 days from 20 July to 15 August in 2017. The largest VTEC MB was observed in the west of the landfall area along the TC moving direction, on the TC landfall day. Our findings provided the evidence that the Hato's landfall over the coast near Hong Kong caused the apparent ionospheric disturbances above the landfall area.
Identification of Characteristic Spatial Scales to Improve the Performance of Analytical Spectral Solutions to the Groundwater Flow Equation
Authors: Perez Gabriel , Gomez‐Velez Jesus D. , Chen Xingyuan , Scheibe T. , Chen Yunxiang , Bao Jie
Published: December 2021

Analytical solutions for the three‐dimensional groundwater flow equation have been widely used to gain insight about subsurface flow structure and as an alternative to computationally expensive numerical models. Of particular interest are solutions that decompose prescribed hydraulic head boundaries (e.g., Dirichlet boundary condition) into a collection of harmonic functions. Previous studies estimate the frequencies and amplitudes of these harmonics with a least‐square approach where the amplitudes are fitted given a pre‐assigned set of frequencies. In these studies, an ad hoc and structured discretization of the frequency domain is typically used, excluding dominant frequencies while assigning importance to spurious frequencies, with significant consequences for estimating the fluxes and residence times. This study demonstrates the advantages of using a pre‐assigned frequency spectrum that targets the dominant frequencies based on rigorous statistical analysis with predefined significance levels. The new approach is tested for three hydrologic conceptualizations: (a) a synthetic periodic basin, (b) synthetic bedforms, and (c) a natural mountainous watershed. The performance of the frequency spectrum selection is compared with exact analytical or approximate numerical solutions. We found that the new approach better describes the fluxes and residence times for Dirichlet boundaries with well‐defined characteristics spatial scales (e.g., periodic basins and bedforms). For more complex scenarios, such as natural mountainous watersheds, both pre‐assigned frequency spectrums present similar performance. The spectral solutions presented here can play a central role in developing reduced‐complexity models for assessing regional water and solute fluxes within mountain watersheds and hyporheic zones.
Single-cell RNA sequencing reveals B cell–related molecular biomarkers for Alzheimer’s disease
Authors: Xiong Liu-Lin , Xue Lu-Lu , Du Ruo-Lan , Niu Rui-Ze , Chen Li , Chen Jie , Hu Qiao , Tan Ya-Xin , Shang Hui-Fang , Liu Jia , Yu Chang-Yin , Wang Ting-Hua
Published: December 2021

In recent years, biomarkers have been integrated into the diagnostic process and have become increasingly indispensable for obtaining knowledge of the neurodegenerative processes in Alzheimer’s disease (AD). Peripheral blood mononuclear cells (PBMCs) in human blood have been reported to participate in a variety of neurodegenerative activities. Here, a single-cell RNA sequencing analysis of PBMCs from 4 AD patients (2 in the early stage, 2 in the late stage) and 2 normal controls was performed to explore the differential cell subpopulations in PBMCs of AD patients. A significant decrease in B cells was detected in the blood of AD patients. Furthermore, we further examined PBMCs from 43 AD patients and 41 normal subjects by fluorescence activated cell sorting (FACS), and combined with correlation analysis, we found that the reduction in B cells was closely correlated with the patients’ Clinical Dementia Rating (CDR) scores. To confirm the role of B cells in AD progression, functional experiments were performed in early-stage AD mice in which fibrous plaques were beginning to appear; the results demonstrated that B cell depletion in the early stage of AD markedly accelerated and aggravated cognitive dysfunction and augmented the Aβ burden in AD mice. Importantly, the experiments revealed 18 genes that were specifically upregulated and 7 genes that were specifically downregulated in B cells as the disease progressed, and several of these genes exhibited close correlation with AD. These findings identified possible B cell-based AD severity, which are anticipated to be conducive to the clinical identification of AD progression.
Methylome-wide association study of antidepressant use in Generation Scotland and the Netherlands Twin Register implicates the innate immune system
Authors: Barbu Miruna C. , Huider Floris , Campbell Archie , Amador Carmen , Adams Mark J. , Lynall Mary-Ellen , Howard David M. , Walker Rosie M. , Morris Stewart W. , Van Dongen Jenny , Porteous David J. , Evans Kathryn L. , Bullmore Edward , Willemsen Gonneke , Boomsma Dorret I. , Whalley Heather C. , McIntosh Andrew M.
Published: December 2021

Antidepressants are an effective treatment for major depressive disorder (MDD), although individual response is unpredictable and highly variable. Whilst the mode of action of antidepressants is incompletely understood, many medications are associated with changes in DNA methylation in genes that are plausibly linked to their mechanisms. Studies of DNA methylation may therefore reveal the biological processes underpinning the efficacy and side effects of antidepressants. We performed a methylome-wide association study (MWAS) of self-reported antidepressant use accounting for lifestyle factors and MDD in Generation Scotland (GS:SFHS,N = 6428, EPIC array) and the Netherlands Twin Register (NTR,N = 2449, 450 K array) and ran a meta-analysis of antidepressant use across these two cohorts. We found ten CpG sites significantly associated with self-reported antidepressant use in GS:SFHS, with the top CpG located within a gene previously associated with mental health disorders,ATP6V1B2(β = −0.055,pcorrected = 0.005). Other top loci were annotated to genes includingCASP10, TMBIM1, MAPKAPK3, andHEBP2, which have previously been implicated in the innate immune response. Next, using penalised regression, we trained a methylation-based score of self-reported antidepressant use in a subset of 3799 GS:SFHS individuals that predicted antidepressant use in a second subset of GS:SFHS (N = 3360,β = 0.377,p = 3.12 × 10−11,R2 = 2.12%). In an MWAS analysis of prescribed selective serotonin reuptake inhibitors, we showed convergent findings with those based on self-report. In NTR, we did not find any CpGs significantly associated with antidepressant use. The meta-analysis identified the two CpGs of the ten above that were common to the two arrays used as being significantly associated with antidepressant use, although the effect was in the opposite direction for one of them. Antidepressants were associated with epigenetic alterations in loci previously associated with mental health disorders and the innate immune system. These changes predicted self-reported antidepressant use in a subset of GS:SFHS and identified processes that may be relevant to our mechanistic understanding of clinically relevant antidepressant drug actions and side effects.
Nucleolar stress controls mutant Huntington toxicity and monitors Huntington’s disease progression
Authors: Sönmez Aynur , Mustafa Rasem , Ryll Salome T. , Tuorto Francesca , Wacheul Ludivine , Ponti Donatella , Litke Christian , Hering Tanja , Kojer Kerstin , Koch Jenniver , Pitzer Claudia , Kirsch Joachim , Neueder Andreas , Kreiner Grzegorz , Lafontaine Denis L. J. , Orth Michael , Liss Birgit , Parlato Rosanna
Published: December 2021

Transcriptional and cellular-stress surveillance deficits are hallmarks of Huntington’s disease (HD), a fatal autosomal-dominant neurodegenerative disorder caused by a pathological expansion of CAG repeats in the Huntingtin (HTT) gene. The nucleolus, a dynamic nuclear biomolecular condensate and the site of ribosomal RNA (rRNA) transcription, is implicated in the cellular stress response and in protein quality control. While the exact pathomechanisms of HD are still unclear, the impact of nucleolar dysfunction on HD pathophysiology in vivo remains elusive. Here we identified aberrant maturation of rRNA and decreased translational rate in association with human mutant Huntingtin (mHTT) expression. The protein nucleophosmin 1 (NPM1), important for nucleolar integrity and rRNA maturation, loses its prominent nucleolar localization. Genetic disruption of nucleolar integrity in vulnerable striatal neurons of the R6/2 HD mouse model decreases the distribution of mHTT in a disperse state in the nucleus, exacerbating motor deficits. We confirmed NPM1 delocalization in the gradually progressing zQ175 knock-in HD mouse model: in the striatum at a presymptomatic stage and in the skeletal muscle at an early symptomatic stage. In Huntington’s patient skeletal muscle biopsies, we found a selective redistribution of NPM1, similar to that in the zQ175 model. Taken together, our study demonstrates that nucleolar integrity regulates the formation of mHTT inclusions in vivo, and identifies NPM1 as a novel, readily detectable peripheral histopathological marker of HD progression.
Genetic dissection for head blast resistance in wheat using two mapping populations
Authors: He Xinyao , Kabir Muhammad Rezaul , Roy Krishna K. , Marza Felix , Chawade Aakash , Duveiller Etienne , Pierre Carolina Saint , Singh Pawan K.
Published: December 2021

Wheat head blast is a dangerous fungal disease in South America and has recently spread to Bangladesh and Zambia, threatening wheat production in those regions. Host resistance as an economical and environment-friendly management strategy has been heavily relied on, and understanding the resistance loci in the wheat genome is very helpful to resistance breeding. In the current study, two recombinant inbred line (RIL) populations, Alondra/Milan (with 296 RILs) and Caninde#2/Milan-S (with 254 RILs and Milan-S being a susceptible variant of Milan), were used for mapping QTL associated with head blast resistance in field experiments. Phenotyping was conducted in Quirusillas and Okinawa, Bolivia, and in Jashore, Bangladesh, during the 2017–18 and 2018–19 cropping cycles. The DArTseq® technology was employed to genotype the lines, along with four STS markers in the 2NS region. A QTL with consistent major effects was mapped on the 2NS/2AS translocation region in both populations, explaining phenotypic variation from 16.7 to 79.4% across experiments. Additional QTL were detected on chromosomes 2DL, 7AL, and 7DS in the Alondra/Milan population, and 2BS, 4AL, 5AS, 5DL, 7AS, and 7AL in the Caninde#2/Milan-S population, all showing phenotypic effects <10%. The results corroborated the important role of the 2NS/2AS translocation on WB resistance and identified a few novel QTL for possible deployment in wheat breeding. The low phenotypic effects of the non-2NS QTL warrantee further investigation for novel QTL with higher and more stable effects against WB, to alleviate the heavy reliance on 2NS-based resistance.
Learning efficient navigation in vortical flow fields
Authors: Gunnarson Peter , Mandralis Ioannis , Novati Guido , Koumoutsakos Petros , Dabiri John O.
Published: December 2021

Efficient point-to-point navigation in the presence of a background flow field is important for robotic applications such as ocean surveying. In such applications, robots may only have knowledge of their immediate surroundings or be faced with time-varying currents, which limits the use of optimal control techniques. Here, we apply a recently introduced Reinforcement Learning algorithm to discover time-efficient navigation policies to steer a fixed-speed swimmer through unsteady two-dimensional flow fields. The algorithm entails inputting environmental cues into a deep neural network that determines the swimmer’s actions, and deploying Remember and Forget Experience Replay. We find that the resulting swimmers successfully exploit the background flow to reach the target, but that this success depends on the sensed environmental cue. Surprisingly, a velocity sensing approach significantly outperformed a bio-mimetic vorticity sensing approach, and achieved a near 100% success rate in reaching the target locations while approaching the time-efficiency of optimal navigation trajectories.
A predominant enhancer co-amplified with the SOX2 oncogene is necessary and sufficient for its expression in squamous cancer
Authors: Liu Yanli , Wu Zhong , Zhou Jin , Ramadurai Dinesh K. A. , Mortenson Katelyn L. , Aguilera-Jimenez Estrella , Yan Yifei , Yang Xiaojun , Taylor Alison M. , Varley Katherine E. , Gertz Jason , Choi Peter S. , Cherniack Andrew D. , Chen Xingdong , Bass Adam J. , Bailey Swneke D. , Zhang Xiaoyang
Published: December 2021

Amplification and overexpression of the SOX2 oncogene represent a hallmark of squamous cancers originating from diverse tissue types. Here, we find that squamous cancers selectively amplify a 3’ noncoding region together with SOX2, which harbors squamous cancer-specific chromatin accessible regions. We identify a single enhancer e1 that predominantly drives SOX2 expression. Repression of e1 in SOX2-high cells causes collapse of the surrounding enhancers, remarkable reduction in SOX2 expression, and a global transcriptional change reminiscent of SOX2 knockout. The e1 enhancer is driven by a combination of transcription factors including SOX2 itself and the AP-1 complex, which facilitates recruitment of the co-activator BRD4. CRISPR-mediated activation of e1 in SOX2-low cells is sufficient to rebuild the e1-SOX2 loop and activate SOX2 expression. Our study shows that squamous cancers selectively amplify a predominant enhancer to drive SOX2 overexpression, uncovering functional links among enhancer activation, chromatin looping, and lineage-specific copy number amplifications of oncogenes.
Synthesis and structure elucidation of the human tRNA nucleoside mannosyl-queuosine
Authors: Hillmeier Markus , Wagner Mirko , Ensfelder Timm , Korytiakova Eva , Thumbs Peter , Müller Markus , Carell Thomas
Published: December 2021

Queuosine (Q) is a structurally complex, non‐canonical RNA nucleoside. It is present in many eukaryotic and bacterial species, where it is part of the anticodon loop of certain tRNAs. In higher vertebrates, including humans, two further modified queuosine-derivatives exist ‐ galactosyl‐ (galQ) and mannosyl-queuosine (manQ). The function of these low abundant hypermodified RNA nucleosides remains unknown. While the structure of galQ was elucidated and confirmed by total synthesis, the reported structure of manQ still awaits confirmation. By combining total synthesis and LC-MS-co-injection experiments, together with a metabolic feeding study of labelled hexoses, we show here that the natural compound manQ isolated from mouse liver deviates from the literature-reported structure. Our data show that manQ features an α‐allyl connectivity of its sugar moiety. The yet unidentified glycosylases that attach galactose and mannose to the Q‐base therefore have a maximally different constitutional connectivity preference. Knowing the correct structure of manQ will now pave the way towards further elucidation of its biological function.
Diblock dialternating terpolymers by one-step/one-pot highly selective organocatalytic multimonomer polymerization
Authors: Xu Jiaxi , Wang Xin , Hadjichristidis Nikos
Published: December 2021

The synthesis of well-defined block copolymers from a mixture of monomers without additional actions (“one-pot/one-step”) is an ideal and industrially valuable method. In addition, the presence of controlled alternating sequences in one or both blocks increases the structural diversity of polymeric materials, but, at the same time, the synthetic difficulty. Here we show that the “one-pot/one-step” ring-opening terpolymerization of a mixture of three monomers (N-sulfonyl aziridines; cyclic anhydrides and epoxides), with tert-butylimino-tris(dimethylamino)phosphorene (t-BuP1) as a catalyst, results in perfect diblock dialternating terpolymers having a sharp junction between the two blocks, with highly-controllable molecular weights and narrow molecular weight distributions (Ð < 1.08). The organocatalyst switches between two distinct polymerization cycles without any external stimulus, showing high monomer selectivity and kinetic control. The proposed mechanism is based on NMR, in-situ FTIR, SEC, MALDI-ToF, reactivity ratios, and kinetics studies.
Helicase Q promotes homology-driven DNA double-strand break repair and prevents tandem duplications
Authors: Kamp J. A. , Lemmens B. B. L. G. , Romeijn R. J. , Changoer S. C. , van Schendel R. , Tijsterman M.
Published: December 2021

DNA double-strand breaks are a major threat to cellular survival and genetic integrity. In addition to high fidelity repair, three intrinsically mutagenic DNA break repair routes have been described, i.e. single-strand annealing (SSA), polymerase theta-mediated end-joining (TMEJ) and residual ill-defined microhomology-mediated end-joining (MMEJ) activity. Here, we identify C. elegans Helicase Q (HELQ-1) as being essential for MMEJ as well as for SSA. We also find HELQ-1 to be crucial for the synthesis-dependent strand annealing (SDSA) mode of homologous recombination (HR). Loss of HELQ-1 leads to increased genome instability: patchwork insertions arise at deletion junctions due to abortive rounds of polymerase theta activity, and tandem duplications spontaneously accumulate in genomes of helq-1 mutant animals as a result of TMEJ of abrogated HR intermediates. Our work thus implicates HELQ activity for all DSB repair modes guided by complementary base pairs and provides mechanistic insight into mutational signatures common in HR-defective cancers.
Acetoacetate protects macrophages from lactic acidosis-induced mitochondrial dysfunction by metabolic reprograming
Authors: Adam Clément , Paolini Léa , Gueguen Naïg , Mabilleau Guillaume , Preisser Laurence , Blanchard Simon , Pignon Pascale , Manero Florence , Le Mao Morgane , Morel Alain , Reynier Pascal , Beauvillain Céline , Delneste Yves , Procaccio Vincent , Jeannin Pascale
Published: December 2021

Lactic acidosis, the extracellular accumulation of lactate and protons, is a consequence of increased glycolysis triggered by insufficient oxygen supply to tissues. Macrophages are able to differentiate from monocytes under such acidotic conditions, and remain active in order to resolve the underlying injury. Here we show that, in lactic acidosis, human monocytes differentiating into macrophages are characterized by depolarized mitochondria, transient reduction of mitochondrial mass due to mitophagy, and a significant decrease in nutrient absorption. These metabolic changes, resembling pseudostarvation, result from the low extracellular pH rather than from the lactosis component, and render these cells dependent on autophagy for survival. Meanwhile, acetoacetate, a natural metabolite produced by the liver, is utilized by monocytes/macrophages as an alternative fuel to mitigate lactic acidosis-induced pseudostarvation, as evidenced by retained mitochondrial integrity and function, retained nutrient uptake, and survival without the need of autophagy. Our results thus show that acetoacetate may increase tissue tolerance to sustained lactic acidosis.
Collapse of the mammoth-steppe in central Yukon as revealed by ancient environmental DNA
Authors: Murchie Tyler J. , Monteath Alistair J. , Mahony Matthew E. , Long George S. , Cocker Scott , Sadoway Tara , Karpinski Emil , Zazula Grant , MacPhee Ross D. E. , Froese Duane , Poinar Hendrik N.
Published: December 2021

The temporal and spatial coarseness of megafaunal fossil records complicates attempts to to disentangle the relative impacts of climate change, ecosystem restructuring, and human activities associated with the Late Quaternary extinctions. Advances in the extraction and identification of ancient DNA that was shed into the environment and preserved for millennia in sediment now provides a way to augment discontinuous palaeontological assemblages. Here, we present a 30,000-year sedimentary ancient DNA (sedaDNA) record derived from loessal permafrost silts in the Klondike region of Yukon, Canada. We observe a substantial turnover in ecosystem composition between 13,500 and 10,000 calendar years ago with the rise of woody shrubs and the disappearance of the mammoth-steppe (steppe-tundra) ecosystem. We also identify a lingering signal of Equus sp. (North American horse) and Mammuthus primigenius (woolly mammoth) at multiple sites persisting thousands of years after their supposed extinction from the fossil record.
Ir-catalyzed enantioselective B−H alkenylation for asymmetric synthesis of chiral-at-cage o‑carboranes
Authors: Cheng Ruofei , Zhang Jie , Zhang Huifang , Qiu Zaozao , Xie Zuowei
Published: December 2021

The asymmetric synthesis of chiral-at-cage o-carboranes, whose chirality is associated with the substitution patterns on the polyhedron, is of great interest as the icosahedral carboranes have wide applications in medicinal and materials chemistry. Herein we report an intermolecular Ir-catalyzed enantioselective B−H alkenylation for efficient and facile synthesis of chiral-at-cage o-carboranes with new skeletons under mild reaction conditions. Generally very good to excellent yields with up to 99% ee can be achieved in this Ir-catalyzed B−H alkenylation. The enantiocontrol model is proposed based on Density Functional Theory calculations in which the use of chiral phosphoramidite ligand is essential for such asymmetric o-carborane B−H alkenylation.
Asthma reduces glioma formation by T cell decorin-mediated inhibition of microglia
Authors: Chatterjee Jit , Sanapala Shilpa , Cobb Olivia , Bewley Alice , Goldstein Andrea K. , Cordell Elizabeth , Ge Xia , Garbow Joel R. , Holtzman Michael J. , Gutmann David H.
Published: December 2021

To elucidate the mechanisms underlying the reduced incidence of brain tumors in children with Neurofibromatosis type 1 (NF1) and asthma, we leverage Nf1 optic pathway glioma (Nf1OPG) mice, human and mouse RNAseq data, and two different experimental asthma models. Following ovalbumin or house dust mite asthma induction at 4–6 weeks of age (WOA), Nf1OPG mouse optic nerve volumes and proliferation are decreased at 12 and 24 WOA, indicating no tumor development. This inhibition is accompanied by reduced expression of the microglia-produced optic glioma mitogen, Ccl5. Human and murine T cell transcriptome analyses reveal that inhibition of microglia Ccl5 production results from increased T cell expression of decorin, which blocks Ccl4-mediated microglia Ccl5 expression through reduced microglia NFκB signaling. Decorin or NFκB inhibitor treatment of Nf1OPG mice at 4–6 WOA inhibits tumor formation at 12 WOA, thus establishing a potential mechanistic etiology for the attenuated glioma incidence observed in children with asthma.
NV– diamond laser
Authors: Savvin Alexander , Dormidonov Alexander , Smetanina Evgeniya , Mitrokhin Vladimir , Lipatov Evgeniy , Genin Dmitriy , Potanin Sergey , Yelisseyev Alexander , Vins Viktor
Published: December 2021

For the first time, lasing at NV−centers in an optically pumped diamond sample is achieved. A nanosecond train of 150-ps 532-nm laser pulses was used to pump the sample. The lasing pulses have central wavelength at 720 nm with a spectrum width of 20 nm, 1-ns duration and total energy around 10 nJ. In a pump-probe scheme, we investigate lasing conditions and gain saturation due to NV−ionization and NV0concentration growth under high-power laser pulse pumping of diamond crystal.
Structural basis for transthyretin amyloid formation in vitreous body of the eye
Authors: Iakovleva Irina , Hall Michael , Oelker Melanie , Sandblad Linda , Anan Intissar , Sauer-Eriksson A. Elisabeth
Published: December 2021

Amyloid transthyretin (ATTR) amyloidosis is characterized by the abnormal accumulation of ATTR fibrils in multiple organs. However, the structure of ATTR fibrils from the eye is poorly understood. Here, we used cryo-EM to structurally characterize vitreous body ATTR fibrils. These structures were distinct from previously characterized heart fibrils, even though both have the same mutation and type A pathology. Differences were observed at several structural levels: in both the number and arrangement of protofilaments, and the conformation of the protein fibril in each layer of protofilaments. Thus, our results show that ATTR protein structure and its assembly into protofilaments in the type A fibrils can vary between patients carrying the same mutation. By analyzing and matching the interfaces between the amino acids in the ATTR fibril with those in the natively folded TTR, we are able to propose a mechanism for the structural conversion of TTR into a fibrillar form.
Wetting ridge assisted programmed magnetic actuation of droplets on ferrofluid-infused surface
Authors: Zhang Jianqiang , Wang Xuejiao , Wang Zhaoyue , Pan Shangfa , Yi Bo , Ai Liqing , Gao Jun , Mugele Frieder , Yao Xi
Published: December 2021

Flexible actuation of droplets is crucial for biomedical and industrial applications. Hence, various approaches using optical, electrical, and magnetic forces have been exploited to actuate droplets. For broad applicability, an ideal approach should be programmable and be able to actuate droplets of arbitrary size and composition. Here we present an “additive-free” magnetic actuation method to programmably manipulate droplets of water, organic, and biological fluids of arbitrary composition, as well as solid samples, on a ferrofluid-infused porous surface. We specifically exploit the spontaneously formed ferrofluid wetting ridges to actuate droplets using spatially varying magnetic fields. We demonstrate programmed processing and analysis of biological samples in individual drops as well as the collective actuation of large ensembles of micrometer-sized droplets. Such model respiratory droplets can be accumulated for improved quantitative and sensitive bioanalysis - an otherwise prohibitively difficult task that may be useful in tracking coronavirus.
Deep-ultraviolet electroluminescence and photocurrent generation in graphene/hBN/graphene heterostructures
Authors: Song Su-Beom , Yoon Sangho , Kim So Young , Yang Sera , Seo Seung-Young , Cha Soonyoung , Jeong Hyeon-Woo , Watanabe Kenji , Taniguchi Takashi , Lee Gil-Ho , Kim Jun Sung , Jo Moon-Ho , Kim Jonghwan
Published: December 2021

Hexagonal boron nitride (hBN) is a van der Waals semiconductor with a wide bandgap of ~ 5.96 eV. Despite the indirect bandgap characteristics of hBN, charge carriers excited by high energy electrons or photons efficiently emit luminescence at deep-ultraviolet (DUV) frequencies via strong electron-phonon interaction, suggesting potential DUV light emitting device applications. However, electroluminescence from hBN has not been demonstrated at DUV frequencies so far. In this study, we report DUV electroluminescence and photocurrent generation in graphene/hBN/graphene heterostructures at room temperature. Tunneling carrier injection from graphene electrodes into the band edges of hBN enables prominent electroluminescence at DUV frequencies. On the other hand, under DUV laser illumination and external bias voltage, graphene electrodes efficiently collect photo-excited carriers in hBN, which generates high photocurrent. Laser excitation micro-spectroscopy shows that the radiative recombination and photocarrier excitation processes in the heterostructures mainly originate from the pristine structure and the stacking faults in hBN. Our work provides a pathway toward efficient DUV light emitting and detection devices based on hBN.
On the possibility that PbZrO3 not be antiferroelectric
Authors: Aramberri Hugo , Cazorla Claudio , Stengel Massimiliano , Íñiguez Jorge
Published: December 2021

Lead zirconate (PbZrO3) is considered the prototypical antiferroelectric material with an antipolar ground state. Yet, several experimental and theoretical works hint at a partially polar behaviour in this compound, indicating that the polarization may not be completely compensated. In this work, we propose a simple ferrielectric structure for lead zirconate. First-principles calculations reveal this state to be more stable than the commonly accepted antiferroelectric phase at low temperatures, possibly up to room temperature, suggesting that PbZrO3 may not be antiferroelectric at ambient conditions. We discuss the implications of our discovery, how it can be reconciled with experimental observations and how the ferrielectric phase could be obtained in practice.
Human skin triglycerides prevent bed bug (Cimex lectularius L.) arrestment
Authors: Gaire Sudip , DeVries Zachary C. , Mick Russell , Santangelo Richard G. , Bottillo Grazia , Camera Emanuela , Schal Coby
Published: December 2021

Bed bugs (Cimex lectularius) have proliferated globally and have become one of the most challenging pests to control indoors. They are nocturnal and use multiple sensory cues to detect and orient towards their human hosts. After feeding, usually on a sleeping human, they return to a shelter on or around the sleeping surface, but not directly on the host. We hypothesized that although human skin odors attract hungry bed bugs, human skin compounds may also prevent arrestment on hosts. We used arrestment assays to test human skin swabs, extracts from human skin swabs, and pure compounds identified from human skin swabs. When given a choice, bed bugs preferred to arrest on substrates not previously conditioned by humans. These responses were consistent among laboratory-reared and apartment-collected bed bugs. The compounds responsible for this behavior were found to be extractable in hexane, and bed bugs responded to such extracts in a dose-dependent manner. Bioassay-guided fractionation paired with thin-layer chromatography, GC–MS, and LC–MS analyses suggested that triglycerides (TAGs), common compounds found on human skin, were preventing arrestment on shelters. Bed bugs universally avoided sheltering in TAG-treated shelters, which was independent of the number of carbons or the number of double bonds in the TAG. These results provide strong evidence that the complex of human skin compounds serve as multifunctional semiochemicals for bed bugs, with some odorants attracting host-seeking stages, and others (TAGs and possibly other compounds) preventing bed bug arrestment. Host chemistry, environmental conditions and the physiological state of bed bugs likely influence the dual nature behavioral responses of bed bugs to human skin compounds.
Platelet-lymphocyte ratio as a new predictor of in-hospital mortality in cardiac intensive care unit patients
Authors: Zhai Guangyao , Wang Jianlong , Liu Yuyang , Zhou Yujie
Published: December 2021

It has been discovered that both inflammation and platelet aggregation could cause crucial effect on the occurrence and development of cardiovascular diseases. As a combination of platelet and lymphocyte, platelet-lymphocyte ratio (PLR) was proved to be correlated with the severity as well as prognosis of cardiovascular diseases. Exploring the relationship between PLR and in-hospital mortality in cardiac intensive care unit (CICU) patients was the purpose of this study. PLR was calculated by dividing platelet count by lymphocyte count. All patients were grouped by PLR quartiles and the primary outcome was in-hospital mortality. The independent effect of PLR was determined by binary logistic regression analysis. The curve in line with overall trend was drawn by local weighted regression (Lowess). Subgroup analysis was used to determine the relationship between PLR and in-hospital mortality in different subgroups. We included 5577 CICU patients. As PLR quartiles increased, in-hospital mortality increased significantly (Quartile 4 vs. Quartile 1: 13.9 vs. 8.3, P < 0.001). After adjusting for confounding variables, PLR was proved to be independently associated with increased risk of in-hospital mortality (Quartile 4 vs. Quartile 1: OR 95% CI 1.55, 1.08–2.21, P = 0.016, P for trend < 0.001). The Lowess curves showed a positive relationship between PLR and in-hospital mortality. The subgroup analysis revealed that patients with low Acute Physiology and Chronic Health Evaluation IV (APACHE IV) or with less comorbidities had higher risk of mortality for PLR. Further, PLR quartiles had positive relation with length of CICU stay (Quartile 4 vs. Quartile 1: 2.7, 1.6–5.2 vs. 2.1, 1.3–3.9, P < 0.001), and the length of hospital stay (Quartile 4 vs. Quartile 1: 7.9, 4.6–13.1 vs. 5.8, 3.3–9.8, P < 0.001). PLR was independently associated with in-hospital mortality in CICU patients.
A food web approach reveals the vulnerability of biocontrol services by birds and bats to landscape modification at regional scale
Authors: Herrera José M. , Silva Bruno , Jiménez-Navarro Gerardo , Barreiro Silvia , Melguizo-Ruiz Nereida , Moreira Francisco , Vasconcelos Sasha , Morgado Rui , Rodriguez-Pérez Javier
Published: December 2021

Pest control services provided by naturally occurring species (the so-called biocontrol services) are widely recognized to provide key incentives for biodiversity conservation. This is particularly relevant for vertebrate-mediated biocontrol services as many vertebrate species are of conservation concern, with most of their decline associated to landscape modification for agricultural purposes. Yet, we still lack rigorous approaches evaluating landscape-level correlates of biocontrol potential by vertebrates over broad spatial extents to better inform land-use and management decisions. We performed a spatially-explicit interaction-based assessment of potential biocontrol services in Portugal, using 1853 pairwise trophic interactions between 78 flying vertebrate species (birds and bats) and 53 insect pests associated to two widespread and economically valuable crops in the Euro-Mediterranean region, olive groves (Olea europaea subsp. europaea) and vineyards (Vitis vinifera subsp. vinifera). The study area was framed using 1004 square cells, each 10 × 10 km in size. Potential biocontrol services were determined at all those 10 × 10 km grid-cells in which each crop was present as the proportion of the realized out of all potential pairwise interactions between vertebrates and pests. Landscape correlates of biocontrol potential were also explored. Our work suggests that both birds and bats can effectively provide biocontrol services in olive groves and vineyards as they prey many insect pest species associated to both crops. Moreover, it demonstrates that these potential services are impacted by landscape-scale features and that this impact is consistent when evaluated over broad spatial extents. Thus, biocontrol potential by vertebrates significantly increases with increasing amount of natural area, while decreases with increasing area devoted to target crops, particularly olive groves. Overall, our study highlights the suitability of our interaction-based approach to perform spatially-explicit assessments of potential biocontrol services by vertebrates at local spatial scales and suggest its utility for integrating biodiversity and ecosystem services in conservation planning over broad spatial extents.
A comparative study of plant volatiles induced by insect and gastropod herbivory
Authors: Mann Leslie , Laplanche Diane , Turlings Ted C. J. , Desurmont Gaylord A.
Published: December 2021

Insect and gastropod herbivores are major plant consumers and their importance in the evolution of plant defensive traits is broadly recognized. However, their respective effects on plant responses have rarely been compared. Here we focused on plant volatile emissions (VOCs) following herbivory and compared the effects of herbivory by caterpillars of the generalist insect Spodoptera littoralis and by generalist slugs of the genus Arion on the VOCs emissions of 14 cultivated plant species. Results revealed that plants consistently produced higher amounts of volatiles and responded more specifically to caterpillar than to slug herbivory. Specifically, plants released on average 6.0 times more VOCs (total), 8.9 times more green leaf volatiles, 4.2 times more terpenoids, 6.0 times more aromatic hydrocarbons, and 5.7 times more other VOCs in response to 1 cm2 of insect damage than to 1 cm2 of slug damage. Interestingly, four of the plant species tested produced a distinct blend of volatiles following insect damage but not slug damage. These findings may result from different chemical elicitors or from physical differences in herbivory by the two herbivores. This study is an important step toward a more inclusive view of plant responses to different types of herbivores.
The effect of eraser sampling for proteomic analysis on Palaeolithic bone surface microtopography
Authors: Sinet-Mathiot Virginie , Martisius Naomi L. , Schulz-Kornas Ellen , van Casteren Adam , Tsanova Tsenka R. , Sirakov Nikolay , Spasov Rosen , Welker Frido , Smith Geoff M. , Hublin Jean-Jacques
Published: December 2021

Bone surface modifications are crucial for understanding human subsistence and dietary behaviour, and can inform about the techniques employed in the production and use of bone tools. Permission to destructively sample such unique artefacts is not always granted. The recent development of non-destructive proteomic extraction techniques has provided some alternatives for the analysis of rare and culturally significant artefacts, including bone tools and personal ornaments. The Eraser Extraction Method (EEM), first developed for ZooMS analysis of parchment, has recently been applied to bone and ivory specimens. To test the potential impact of the EEM on ancient bone surfaces, we analyse six anthropogenically modified Palaeolithic bone specimens from Bacho Kiro Cave (Bulgaria) through a controlled sampling experiment using qualitative and 3D quantitative microscopy. Although the overall bone topography is generally preserved, our findings demonstrate a slight flattening of the microtopography alongside the formation of micro-striations associated with the use of the eraser for all bone specimens. Such modifications are similar to ancient use-wear traces. We therefore consider the EEM a destructive sampling approach for Palaeolithic bone surfaces. Together with low ZooMS success rates in some of the reported studies, the EEM might not be a suitable approach to taxonomically identify Pleistocene bone specimens.
Robust, fiducial-free drift correction for super-resolution imaging
Authors: Wester Michael J. , Schodt David J. , Mazloom-Farsibaf Hanieh , Fazel Mohamadreza , Pallikkuth Sandeep , Lidke Keith A.
Published: December 2021

We describe a robust, fiducial-free method of drift correction for use in single molecule localization-based super-resolution methods. The method combines periodic 3D registration of the sample using brightfield images with a fast post-processing algorithm that corrects residual registration errors and drift between registration events. The method is robust to low numbers of collected localizations, requires no specialized hardware, and provides stability and drift correction for an indefinite time period.
Emergence of novel combinations of SARS-CoV-2 spike receptor binding domain variants in Senegal
Authors: Ahouidi Ambroise D. , Rodgers Mary A. , Padane Abdou , Leye Nafissatou , Olivo Ana , Mbow Moustapha , Mboup Aminata , Diaw Papa Alassane , Dia Aminata , Harris Barbara , Padane Yacine Amet Dia , Lo Gora , Meyer Todd V. , Diedhiou Cyrille K. , Diagne Diabou , Kane Ndeye Coumba Toure , Cloherty Gavin , Mboup Souleymane
Published: December 2021

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineages that carry mutations in the spike gene are of concern for potential impact to treatment and prevention efforts. To monitor for new SARS-CoV-2 mutations, a panel of specimens were sequenced from both wave one (N = 96), and wave two (N = 117) of the pandemic in Senegal by whole genome next generation sequencing. Amongst these genomes, new combinations of SARS-CoV-2 spike mutations were identified, with E484K + N501T, L452R + N501Y, and L452M + S477N exclusively found in second wave specimens. These sequences are evidence of local diversification over the course of the pandemic and parallel evolution of escape mutations in different lineages.
Single-cell mapping of DNA G-quadruplex structures in human cancer cells
Authors: Hui Winnie W. I. , Simeone Angela , Zyner Katherine G. , Tannahill David , Balasubramanian Shankar
Published: December 2021

G-quadruplexes (G4s) are four-stranded DNA secondary structures that form in guanine-rich regions of the genome. G4s have important roles in transcription and replication and have been implicated in genome instability and cancer. Thus far most work has profiled the G4 landscape in an ensemble of cell populations, therefore it is critical to explore the structure–function relationship of G4s in individual cells to enable detailed mechanistic insights into G4 function. With standard ChIP-seq methods it has not been possible to determine if G4 formation at a given genomic locus is variable between individual cells across a population. For the first time, we demonstrate the mapping of a DNA secondary structure at single-cell resolution. We have adapted single-nuclei (sn) CUT&Tag to allow the detection of G4s in single cells of human cancer cell lines. With snG4-CUT&Tag, we can distinguish cellular identity from a mixed cell-type population solely based on G4 features within individual cells. Our methodology now enables genomic investigations on cell-to-cell variation of a DNA secondary structure that were previously not possible.
Effects of endocannabinoids on feed intake, stress response and whole-body energy metabolism in dairy cows
Authors: van Ackern Isabel , Wulf Ramona , Dannenberger Dirk , Tuchscherer Armin , Kuhla Björn
Published: December 2021

Endocannabinoids, particularly anandamide (AEA) and 2-arachidonoylglycerol (2-AG), are instrumental in regulating energy homeostasis and stress response. However, little is known about the endocannabinoid system (ECS) in ruminants, although EC could improve dairy health and productivity, at least by increasing feed intake. In this study, we report if intraperitoneal (i.p.) AEA and 2-AG administration affects feed intake, whole-body macronutrient metabolism, isolation and restraint stress, and whether diet composition modulates circulating endocannabinoid concentrations in cows. Twenty Simmental cows in late lactation were fed a grass silage and a corn silage based diet. On each diet, cows received daily i.p. injections with either AEA (5 µg/kg; n = 7), 2-AG (2.5 µg/kg; n = 6) or saline (n = 7) for 8 days. Endocannabinoid administration for 5 days under free-ranging (non-stressed) conditions had no effect on feed intake or energy balance, but attenuated the stress-induced suppression of feed intake when housing changed to individual tie-stalls without social or tactile interaction. Endocannabinoids increased whole-body carbohydrate oxidation, reduced fat oxidation, and affected plasma non-esterified fatty acid concentrations and fatty acid contents of total lipids. There was no effect of endocannabinoids on plasma triglyceride concentrations or hepatic lipogenesis. Plasma AEA concentrations were not affected by diet, however, plasma 2-AG concentrations tended to be lower on the corn silage based diet. In conclusion, endocannabinoids attenuate stress-induced hypophagia, increase short-term feed intake and whole-body carbohydrate oxidation and decrease whole-body fat oxidation in cows.
Intraoperative discrimination of native meningioma and dura mater by Raman spectroscopy
Authors: Jelke Finn , Mirizzi Giulia , Borgmann Felix Kleine , Husch Andreas , Slimani Rédouane , Klamminger Gilbert Georg , Klein Karoline , Mombaerts Laurent , Gérardy Jean-Jacques , Mittelbronn Michel , Hertel Frank
Published: December 2021

Meningiomas are among the most frequent tumors of the central nervous system. For a total resection, shown to decrease recurrences, it is paramount to reliably discriminate tumor tissue from normal dura mater intraoperatively. Raman spectroscopy (RS) is a non-destructive, label-free method for vibrational analysis of biochemical molecules. On the microscopic level, RS was already used to differentiate meningioma from dura mater. In this study we test its suitability for intraoperative macroscopic meningioma diagnostics. RS is applied to surgical specimen of intracranial meningiomas. The main purpose is the differentiation of tumor from normal dura mater, in order to potentially accelerate the diagnostic workflow. The collected meningioma and dura mater samples (n = 223 tissue samples from a total of 59 patients) are analyzed under untreated conditions using a new partially robotized RS acquisition system. Spectra (n = 1273) are combined with the according histopathological analysis for each sample. Based on this, a classifier is trained via machine learning. Our trained classifier separates meningioma and dura mater with a sensitivity of 96.06 $$\pm $$
±
0.03% and a specificity of 95.44 $$\pm $$
±
0.02% for internal fivefold cross validation and 100% and 93.97% if validated with an external test set. RS is an efficient method to discriminate meningioma from healthy dura mater in fresh tissue samples without additional processing or histopathological imaging. It is a quick and reliable complementary diagnostic tool to the neuropathological workflow and has potential for guided surgery. RS offers a safe way to examine unfixed surgical specimens in a perioperative setting.
Cellular heterogeneity of circulating CD4+CD8+ double-positive T cells characterized by single-cell RNA sequencing
Authors: Choi Sung Min , Park Hi Jung , Choi Eun A. , Jung Kyeong Cheon , Lee Jae Il
Published: December 2021

Circulating CD4+CD8+ double-positive (DP) T cells are associated with a variety of disease states. However, unlike conventional T cells, the composition of this population is poorly understood. Here, we used single-cell RNA sequencing (scRNA-seq) to analyze the composition and characteristics of the DP T cell population circulating in the peripheral blood of cynomolgus monkeys. We found that circulating DP T cells not only contain a large number of naïve cells, but also comprise a heterogeneous population (CD4 CTL-, Eomes+ Tr1-, Th2-, Th17-, Tfh-, Treg-, CD8 CTL-, and innate-like cells) with multiple potential functions. Flow cytometry analysis revealed that a substantial number of the naïve DP T cells expressed CD8αβ, as well as CD8αα, along with high expression of CD31. Moreover, the CD4hiCD8lo and CD4hiCD8hi populations, which express high levels of the CD4 coreceptor, comprised subsets characterized by helper and regulatory functions, some of which also exhibited cytotoxic functions. By contrast, the CD4loCD8hi population with high CD8 coreceptor expression comprised a subset characterized by CD8 CTL- and innate-like properties. Taken together, the data show that scRNA-seq analysis identified a more diverse subset of the circulating DP cells than is currently known, despite this population being very small.