bluuebunny/crossref_metadata_2025 huggingface dataset:
A Microbial‐Explicit Soil Organic Carbon Decomposition Model (MESDM): Development and Testing at a Semiarid Grassland Site
Authors: Zhang Xia , Xie Zhenghui , Ma Zhuguo , Barron‐Gafford Greg A. , Scott Russell L. , Niu Guo‐Yue
Published: January 2022

Explicit representations of microbial processes in soil organic carbon (SOC) decomposition models have received increasing attention, because soil heterotrophic respiration remains one of the greatest uncertainties in climate‐carbon feedbacks projected by Earth system models (ESMs). Microbial‐explicit models have been developed and applied in site‐ and global‐scale studies. These models, however, lack the ability to represent microbial respiration responses to drying‐wetting cycles, and few of them have been incorporated in land surface models (LSMs) and validated against field observations. In this study, we developed a multi‐layer, microbial‐explicit soil organic carbon decomposition model (MESDM), based on two main assumptions that (a) extracellular enzymes remain active at dry reaction microsites, and (b) microbes at wet microsites are active or potentially active, while microbes at the dry microsites are dormant, by dividing the soil volume into wet and dry zones. MESDM with O2 and CO2 gas transport models was coupled with Noah‐MP LSM and tested against half‐hourly field observations at a semiarid grassland site in the southwest US characterized by pulsed precipitation. The results show MESDM can reproduce the observed soil respiration pulses of various sizes in response to discrete precipitation events (Birch effect) and thus improve the simulation of net ecosystem exchange. Here, both microbial accessibility to accumulated dissolved organic carbon and reactivation of dormant microbes at the dry microsites upon rewetting are critical to reproducing the Birch effect. This study improves our understanding of and ability to simulate complex soil carbon dynamics that experience drying‐wetting cycle in climate‐carbon feedbacks.
From Crystals to Crustal‐Scale Seismic Anisotropy: Bridging the Gap Between Rocks and Seismic Studies With Digital Geologic Map Data in Colorado
Authors: Frothingham Michael G. , Mahan Kevin H. , Schulte‐Pelkum Vera , Caine Jonathan Saul , Vollmer Frederick W.
Published: January 2022

Deep continental crustal structures are enigmatic due to lack of direct exposures and limited tools to investigate them remotely. Seismic waves can sample these rocks, but most seismic methods focus on coarse crustal structures while laboratory measurements concentrate on crystal‐scale rock properties, and little work has been conducted to bridge this interpretation gap. In some places, geologic maps of crystalline basement provide samples of the intermediate‐scale fabrics and structures that may represent in situ deep crust. However, previous research has not considered natural geometric variations from map data, nor is this heterogeneity typically included in map‐scale seismic property calculations. Here, we test how map‐scale fabrics influence crustal seismic anisotropy in Colorado by analyzing structural data from geologic maps, combining those data with bulk rock elastic tensors to calculate map‐scale seismic properties, and evaluating the resulting comparisons with observed receiver function A1 (360° periodic) arrivals. Crystalline fabrics, predicted seismic properties, and tectonic structures positively correlate with shallow and deep crustal A1 arrivals. Additionally, widespread correlations occur between mapped fault traces and regional foliations, implying that preexisting mechanical heterogeneity may have strongly influenced subsequent reactivation. We interpret that various mapped geologic contact types (e.g., lithologic and structural) generate A1 arrivals and that multiple parallel features (e.g., faults, foliations, and intrusions) contribute to a seismically visible tectonic grain. Therefore, Colorado's exhumed basement, as expressed in outcrops and maps, offers insight into modern deep crustal geological and geophysical structure.
Water Footprints, Intra‐National Virtual Water Flows, and Associated Sustainability Related to Pork Production and Consumption: A Case for China
Authors: Ji Xiangxiang , Xie Dong , Zhuo La , Liu Yilin , Feng Bianbian , Wu Pute
Published: January 2022

Growth in water consumption with intensified virtual water (VW) flows from increased production and consumption of both meat and feed crops threatens the sustainability of water resources in water‐scarce countries and export regions. However, a sustainability assessment of both water footprints (WFs) and VW flows related to animal products at a subnational scale is lacking. Here we estimate direct and indirect WFs as well as the inter‐provincial VW flows associated with pork production and consumption in China for the years 2008 and 2017. The contributions of feed crop production and consumption were identified. Both life cycle assessment and WF network frameworks were applied to evaluate the sustainability of blue WF and VW flows. Results show that the national annual consumptive (green‐blue) WF and degradative (gray) WF of pork production increased by 8.7% and 15.8%, respectively. More than 80% of the blue WF in pork production was unsustainable. By 2017, 62% of the unsustainable blue WF and 64% of the water scarcity footprints of pork production in the south resulted from consuming the feed crops from the north. This analysis highlights the importance and provides feasible approaches to uncover remote geographical effects on regional water scarcities from different steps in the value chains of livestock products.
Phase Diversity Electro-optic Sampling: A new approach to single-shot terahertz waveform recording
Authors: Roussel Eléonore , Szwaj Christophe , Evain Clément , Steffen Bernd , Gerth Christopher , Jalali Bahram , Bielawski Serge
Published: January 2022

Recording electric field evolution in single-shot with THz bandwidth is needed in science including spectroscopy, plasmas, biology, chemistry, Free-Electron Lasers, accelerators, and material inspection. However, the potential application range depends on the possibility to achieve sub-picosecond resolution over a long time window, which is a largely open problem for single-shot techniques. To solve this problem, we present a new conceptual approach for the so-called spectral decoding technique, where a chirped laser pulse interacts with a THz signal in a Pockels crystal, and is analyzed using a grating optical spectrum analyzer. By borrowing mathematical concepts from photonic time stretch theory and radio-frequency communication, we deduce a novel dual-output electro-optic sampling system, for which the input THz signal can be numerically retrieved—with unprecedented resolution—using the so-called phase diversity technique. We show numerically and experimentally that this approach enables the recording of THz waveforms in single-shot over much longer durations and/or higher bandwidth than previous spectral decoding techniques. We present and test the proposed DEOS (Diversity Electro-Optic Sampling) design for recording 1.5 THz bandwidth THz pulses, over 20 ps duration, in single-shot. Then we demonstrate the potential of DEOS in accelerator physics by recording, in two successive shots, the shape of 200 fs RMS relativistic electron bunches at European X-FEL, over 10 ps recording windows. The designs presented here can be used directly for accelerator diagnostics, characterization of THz sources, and single-shot Time-Domain Spectroscopy.
Delivering on the promise of early detection with liquid biopsies
Authors: Crosby David
Published: January 2022

Liquid biopsy approaches are relatively well developed for cancer therapy monitoring and disease relapse, but they also have incredible potential in the cancer early detection and screening field. There are, however, several challenges to overcome before this potential can be met. Research in this area needs to be cohesive and, as a driver of research, Cancer Research UK is in an ideal position to enable this.
MicroRNA-149 suppresses osteogenic differentiation of mesenchymal stem cells via inhibition of AKT1-dependent Twist1 phosphorylation
Authors: Fan Jingzhang , Li Shiming , Wang Dawei
Published: January 2022

Osteogenic differentiation is a vital process for growth, repair, and remodeling of bones. Accumulating evidence have suggested that microRNAs (miRNAs or miRs) play a crucial role in osteogenic differentiation of mesenchymal stem cells (MSCs). Hence, the current study set out to elucidate the role of miR-149 in osteogenic differentiation of MSCs and the underlying mechanism. First, rat models of bone differentiation were established using the Masquelet-induced membrane technique, and MSCs were isolated. The expression of miR-149 and AKT1 in the rats and cells was detected with RT-qPCR and western blot analysis. The relationships among miR-149, AKT1, and Twist1 were further predicted by online bioinformatics prediction and verified using dual luciferase reporter gene assay. Alteration of miR-149, AKT1, or Twist1 was performed to further explore their effect on osteogenic differentiation of MSCs. miR-149 was poorly expressed in the process of osteogenic differentiation of MSCs, while AKT1 was highly expressed. miR-149 negatively regulated the expression of AKT1, which in turn diminished the protein levels of Twist1 and promoted the phosphorylation levels of Twist1. Lastly, miR-149 acted as an inhibitor of osteogenic differentiation of MSCs, which could be reversed by AKT1. To sum up, miR-149 silencing promoted osteogenic differentiation of MSCs by enhancing Twist1 degradation through AKT1 upregulation, representing a new method for bone repair treatment.
Knockdown of NRMT enhances sensitivity of retinoblastoma cells to cisplatin through upregulation of the CENPA/Myc/Bcl2 axis
Authors: Li Zhongrui , Zhang Lan , Liu Dongrui , Yang Zhanghui , Xuan Di , Zhang Yi
Published: January 2022

Chemotherapy resistance of tumor cells causes failure in anti-tumor therapies. Recently, N-terminal regulator of chromatin condensation 1 methyltransferase (NRMT) is abnormally expressed in different cancers. Hence, we speculate that NRMT may pay a crucial role in the development of chemosensitivity in retinoblastoma. We characterized the upregulation of NRMT in the developed cisplatin (CDDP)-resistant retinoblastoma cell line relative to parental cells. Loss-of-function experiments demonstrated that NRMT silencing enhanced chemosensitivity of retinoblastoma cells to CDDP. Next, NRMT was identified to enrich histone-H3 lysine 4 trimethylation in the promoter of centromere protein A (CENPA) by chromatin immunoprecipitation assay. Rescue experiments suggested that CENPA reduced chemosensitivity by increasing the viability and proliferation and reducing apoptosis of CDDP-resistant retinoblastoma cells, which was reversed by NRMT. Subsequently, CENPA was witnessed to induce the transcription of Myc and to elevate the expression of B cell lymphoma-2. At last, in vivo experiments confirmed the promotive effect of NRMT knockdown on chemosensitivity of retinoblastoma cells to CDDP in tumor-bearing mice. Taken together, NRMT is an inhibitor of chemosensitivity in retinoblastoma. Those findings shed new light on NRMT-targeted therapies for retinoblastoma.
The involvement of the circFOXM1–miR–432–Gα12 axis in glioma cell proliferation and aggressiveness
Authors: Gong Yong , Zhang Shuai , Wang HongXin , Huang Yunfeng , Fu Xing , Xiang Peng , Fan Tianyu
Published: January 2022

Accumulating evidence indicates that circFOXM1 (Hsa_circ_0025033) is highly expressed in several cancers; however, the function of circFOXM1 in glioma and the molecular mechanism have not been well explored. In the present study, we found that expression of circFOXM1 was upregulated in both glioma tissues and cell lines. In addition, circFOXM1 knockdown suppressed glioma-cell proliferation, activated apoptosis in vitro, and repressed tumour growth in vivo. Moreover, we clarified that circFOXM1 binds with miR-432, which was downregulated in glioma cells. Furthermore, we indicated that Gα12, a direct target of miR-432, was highly expressed in glioma cells, and Gα12 silencing might limit the progression of glioma. Rescue assays indicated that Gα12 reversed the inhibitory effect of circFOXM1 silencing on glioma-cell tumorigenesis. In conclusion, circFOXM1 acts as a sponge of miR-432 to promote the proliferation and aggressiveness of glioma cells through the Gα12 signalling pathway.
Transcription Factor Activation Profiles (TFAP) identify compounds promoting differentiation of Acute Myeloid Leukemia cell lines
Authors: Riccio Federica , Micarelli Elisa , Secci Riccardo , Giuliani Giulio , Vumbaca Simone , Massacci Giorgia , Castagnoli Luisa , Fuoco Claudia , Cesareni Gianni
Published: January 2022

Repurposing of drugs for new therapeutic use has received considerable attention for its potential to limit time and cost of drug development. Here we present a new strategy to identify chemicals that are likely to promote a desired phenotype. We used data from the Connectivity Map (CMap) to produce a ranked list of drugs according to their potential to activate transcription factors that mediate myeloid differentiation of leukemic progenitor cells. To validate our strategy, we tested the in vitro differentiation potential of candidate compounds using the HL-60 human cell line as a myeloid differentiation model. Ten out of 22 compounds, which were ranked high in the inferred list, were confirmed to promote significant differentiation of HL-60. These compounds may be considered candidate for differentiation therapy. The method that we have developed is versatile and it can be adapted to different drug repurposing projects.
Penile surgery for patients with Peyronie’s disease initially treated with collagenase clostridium histolyticum or surgery: a claims database analysis
Authors: Trost Landon , Huang Huan , Han Xu , Burudpakdee Chakkarin , Hu Yiqun
Published: January 2022

Collagenase clostridium histolyticum (CCH) is an injectable therapy targeting collagen present in penile plaques in Peyronie’s disease (PD). Data comparing CCH to penile surgery are limited, and long-term therapeutic outcomes are unknown. This retrospective analysis used a US claims database (January 2014–June 2017) to determine the percentage of men with subsequent penile surgery among those who initially received CCH (n = 1227) or surgery (index treatment; n = 620) for PD. Eligible patients were aged ≥18 years with continuous enrollment ≥6 months before and ≥12 months after index treatment date. During 12 months of post-index treatment follow-up, fewer patients with PD initially treated with CCH (4.6% [56/1227]) had subsequent penile surgery versus those initially treated with penile surgery (10.3% [64/620]; p < 0.0001). Mean ± SD time to first subsequent surgery after initial PD treatment was longer in the CCH versus surgery cohort (7.7 ± 3.0 vs 1.7 ± 3.2 months). The likelihood of subsequent surgery varied by initial surgery type: 18.2% after plaque incision or excision with grafting; 11.6% after penile implant; and 8.2% after tunical plication. Patients with PD who received CCH first were less likely to undergo subsequent surgery compared with those who received surgery first within a 12-month post-treatment follow-up.
Effects of neoadjuvant trastuzumab, pertuzumab and palbociclib on Ki67 in HER2 and ER-positive breast cancer
Authors: Gianni Luca , Colleoni Marco , Bisagni Giancarlo , Mansutti Mauro , Zamagni Claudio , Del Mastro Lucia , Zambelli Stefania , Bianchini Giampaolo , Frassoldati Antonio , Maffeis Ilaria , Valagussa Pinuccia , Viale Giuseppe
Published: January 2022

The crosstalk between estrogen and HER2 receptors and cell-cycle regulation sustains resistance to endocrine therapy of HER2- and hormone receptor-positive breast cancer. We earlier reported that women with HER2 and ER-positive breast cancer receiving neoadjuvant dual HER2-block and palbociclib in the NA-PHER2 trial had Ki67 decrease and 27% pathological complete responses (pCR). We extended NA-PHER2 to Cohort B using dual HER2-block and palbociclib without fulvestrant and report here Ki67 drops at week-2 (mean change −25.7), at surgery (after 16 weeks, mean change −9.5), high objective response (88.5%) and pCR (19.2%). In Cohort C [Ki67 > 20% and HER2low (IHC 1+/2+ without gene amplification)], women also received fulvestrant, had dramatic Ki67 drop at week 2 (−29.5) persisting at surgery (−19.3), and objective responses in 78.3%. In view of the favorable tolerability and of the efficacy-predictive value of Ki67 drop at week-2, the chemotherapy-free approach of NA-PHER2 deserves further investigation in HER2 and ER-positive breast cancer. The trial is registered with ClinicalTrials.gov, number NCT02530424.
First-principles search of hot superconductivity in La-X-H ternary hydrides
Authors: Di Cataldo Simone , von der Linden Wolfgang , Boeri Lilia
Published: January 2022

Motivated by the recent claim of hot superconductivity with critical temperatures up to 550 K in La + x hydrides, we investigate the high-pressure phase diagram of compounds that may have formed in the experiment, using first-principles calculations for evolutionary crystal structure prediction and superconductivity. Starting from the hypothesis that the observed Tc may be realized by successive heating upon a pre-formed LaH10 phase, we examine plausible ternaries of lanthanum, hydrogen and other elements present in the diamond anvil cell: boron, nitrogen, carbon, platinum, gallium, gold. We find that only boron and, to a lesser extent, gallium form metastable superhydride-like structures that can host high-Tc superconductivity, but the predicted Tc’s are incompatible with the experimental reports. Our results indicate that, while the claims of hot superconductivity should be reconsidered, it is very likely that unknown H-rich ternary or multinary phases containing lanthanum, hydrogen, and possibly boron or gallium may have formed under the reported experimental conditions, and that these may exhibit superconducting properties comparable, or even superior, to those of currently known hydrides.
Cofilin 1 promotes the pathogenicity and transmission of pathological α-synuclein in mouse models of Parkinson’s disease
Authors: Yan Mingmin , Xiong Min , Dai Lijun , Zhang Xingyu , Zha Yunhong , Deng Xiaorong , Yu Zhui , Zhang Zhentao
Published: January 2022

The pathological hallmark of Parkinson’s disease (PD) is the presence of Lewy bodies (LBs) with aggregated α-synuclein being the major component. The abnormal α-synuclein aggregates transfer between cells, recruit endogenous α-synuclein into toxic LBs, and finally trigger neuronal injury. However, the molecular mechanisms mediating the aggregation and transmission of pathological α-synuclein remain unknown. Previously we found that cofilin 1, a member of the actin-binding protein, promotes the aggregation and pathogenicity of α-synuclein in vitro. Here we further investigated the effect of cofilin 1 in mouse models of PD. We found that the mixed fibrils composed of cofilin 1 and α-synuclein are more pathogenic to mice and more prone to propagation than pure α-synuclein fibrils. Overexpression of cofilin 1 enhances the seeding and spreading of α-synuclein aggregates, and induces PD-like behavioral impairments in mice. Together, these results illustrate the important role of cofilin 1 in the pathogenicity and transmission of α-synuclein during the onset and progression of PD.
Lewy body disease or diseases with Lewy bodies?
Authors: Menšíková Kateřina , Matěj Radoslav , Colosimo Carlo , Rosales Raymond , Tučková Lucie , Ehrmann Jiří , Hraboš Dominik , Kolaříková Kristýna , Vodička Radek , Vrtěl Radek , Procházka Martin , Nevrlý Martin , Kaiserová Michaela , Kurčová Sandra , Otruba Pavel , Kaňovský Petr
Published: January 2022

The current nosological concept of α-synucleinopathies characterized by the presence of Lewy bodies (LBs) includes Parkinson’s disease (PD), Parkinson’s disease dementia (PDD), and dementia with Lewy bodies (DLB), for which the term “Lewy body disease” (LBD) has recently been proposed due to their considerable clinical and pathological overlap. However, even this term does not seem to describe the true nature of this group of diseases. The subsequent discoveries of α-synuclein (αSyn), SNCA gene, and the introduction of new immunohistochemical methods have started intensive research into the molecular-biological aspects of these diseases. In light of today’s knowledge, the role of LBs in the pathogenesis and classification of these nosological entities remains somewhat uncertain. An increasingly more important role is attributed to other factors as the presence of various LBs precursors, post-translational αSyn modifications, various αSyn strains, the deposition of other pathological proteins (particularly β-amyloid), and the discovery of selective vulnerability of specific cells due to anatomical configuration or synaptic dysfunction. Resulting genetic inputs can undoubtedly be considered as the main essence of these factors. Molecular–genetic data indicate that not only in PD but also in DLB, a unique genetic architecture can be ascertained, predisposing to the development of specific disease phenotypes. The presence of LBs thus remains only a kind of link between these disorders, and the term “diseases with Lewy bodies” therefore results somewhat more accurate.
Parameter estimation in quantum sensing based on deep reinforcement learning
Authors: Xiao Tailong , Fan Jianping , Zeng Guihua
Published: January 2022

Parameter estimation is a pivotal task, where quantum technologies can enhance precision greatly. We investigate the time-dependent parameter estimation based on deep reinforcement learning, where the noise-free and noisy bounds of parameter estimation are derived from a geometrical perspective. We propose a physical-inspired linear time-correlated control ansatz and a general well-defined reward function integrated with the derived bounds to accelerate the network training for fast generating quantum control signals. In the light of the proposed scheme, we validate the performance of time-dependent and time-independent parameter estimation under noise-free and noisy dynamics. In particular, we evaluate the transferability of the scheme when the parameter has a shift from the true parameter. The simulation showcases the robustness and sample efficiency of the scheme and achieves the state-of-the-art performance. Our work highlights the universality and global optimality of deep reinforcement learning over conventional methods in practical parameter estimation of quantum sensing.
Efficacy and immunogenicity of MultiTEP-based DNA vaccines targeting human α-synuclein: prelude for IND enabling studies
Authors: Kim Changyoun , Hovakimyan Armine , Zagorski Karen , Antonyan Tatevik , Petrushina Irina , Davtyan Hayk , Chailyan Gor , Hasselmann Jonathan , Iba Michiyo , Adame Anthony , Rockenstein Edward , Szabo Marcell , Blurton-Jones Mathew , Cribbs David H. , Ghochikyan Anahit , Masliah Eliezer , Agadjanyan Michael G.
Published: January 2022

Accumulation of misfolded proteins such as amyloid-β (Aβ), tau, and α-synuclein (α-Syn) in the brain leads to synaptic dysfunction, neuronal damage, and the onset of relevant neurodegenerative disorder/s. Dementia with Lewy bodies (DLB) and Parkinson’s disease (PD) are characterized by the aberrant accumulation of α-Syn intracytoplasmic Lewy body inclusions and dystrophic Lewy neurites resulting in neurodegeneration associated with inflammation. Cell to cell propagation of α-Syn aggregates is implicated in the progression of PD/DLB, and high concentrations of anti-α-Syn antibodies could inhibit/reduce the spreading of this pathological molecule in the brain. To ensure sufficient therapeutic concentrations of anti-α-Syn antibodies in the periphery and CNS, we developed four α-Syn DNA vaccines based on the universal MultiTEP platform technology designed especially for the elderly with immunosenescence. Here, we are reporting on the efficacy and immunogenicity of these vaccines targeting three B-cell epitopes of hα-Syn aa85–99 (PV-1947D), aa109–126 (PV-1948D), aa126–140 (PV-1949D) separately or simultaneously (PV-1950D) in a mouse model of synucleinopathies mimicking PD/DLB. All vaccines induced high titers of antibodies specific to hα-Syn that significantly reduced PD/DLB-like pathology in hα-Syn D line mice. The most significant reduction of the total and protein kinase resistant hα-Syn, as well as neurodegeneration, were observed in various brain regions of mice vaccinated with PV-1949D and PV-1950D in a sex-dependent manner. Based on these preclinical data, we selected the PV-1950D vaccine for future IND enabling preclinical studies and clinical development.
Moist convection drives an upscale energy transfer at Jovian high latitudes
Authors: Siegelman Lia , Klein Patrice , Ingersoll Andrew P. , Ewald Shawn P. , Young William R. , Bracco Annalisa , Mura Alessandro , Adriani Alberto , Grassi Davide , Plainaki Christina , Sindoni Giuseppe
Published: January 2022

Jupiter’s atmosphere is one of the most turbulent places in the solar system. Whereas observations of lightning and thunderstorms point to moist convection as a small-scale energy source for Jupiter’s large-scale vortices and zonal jets, this has never been demonstrated due to the coarse resolution of pre-Juno measurements. The Juno spacecraft discovered that Jovian high latitudes host a cluster of large cyclones with diameter of around 5,000 km, each associated with intermediate- (roughly between 500 and 1,600 km) and smaller-scale vortices and filaments of around 100 km. Here, we analyse infrared images from Juno with a high resolution of 10 km. We unveil a dynamical regime associated with a significant energy source of convective origin that peaks at 100 km scales and in which energy gets subsequently transferred upscale to the large circumpolar and polar cyclones. Although this energy route has never been observed on another planet, it is surprisingly consistent with idealized studies of rapidly rotating Rayleigh–Bénard convection, lending theoretical support to our analyses. This energy route is expected to enhance the heat transfer from Jupiter’s hot interior to its troposphere and may also be relevant to the Earth’s atmosphere, helping us better understand the dynamics of our own planet.
Observation of a reduced-turbulence regime with boron powder injection in a stellarator
Authors: Nespoli F. , Masuzaki S. , Tanaka K. , Ashikawa N. , Shoji M. , Gilson E. P. , Lunsford R. , Oishi T. , Ida K. , Yoshinuma M. , Takemura Y. , Kinoshita T. , Motojima G. , Kenmochi N. , Kawamura G. , Suzuki C. , Nagy A. , Bortolon A. , Pablant N. A. , Mollen A. , Tamura N. , Gates D. A. , Morisaki T.
Published: January 2022

In state-of-the-art stellarators, turbulence is a major cause of the degradation of plasma confinement. To maximize confinement, which eventually determines the amount of nuclear fusion reactions, turbulent transport needs to be reduced. Here we report the observation of a confinement regime in a stellarator plasma that is characterized by increased confinement and reduced turbulent fluctuations. The transition to this regime is driven by the injection of submillimetric boron powder grains into the plasma. With the line-averaged electron density being kept constant, we observe a substantial increase of stored energy and electron and ion temperatures. At the same time, the amplitude of the plasma turbulent fluctuations is halved. While lower frequency fluctuations are damped, higher frequency modes in the range between 100 and 200 kHz are excited. We have observed this regime for different heating schemes, namely with both electron and ion cyclotron resonant radio frequencies and neutral beams, for both directions of the magnetic field and both hydrogen and deuterium plasmas.
A taxonomic, genetic and ecological data resource for the vascular plants of Britain and Ireland
Authors: Henniges Marie C. , Powell Robyn F. , Mian Sahr , Stace Clive A. , Walker Kevin J. , Gornall Richard J. , Christenhusz Maarten J. M. , Brown Max R. , Twyford Alex D. , Hollingsworth Peter M. , Jones Laura , de Vere Natasha , Antonelli Alexandre , Leitch Andrew R. , Leitch Ilia J.
Published: January 2022

The vascular flora of Britain and Ireland is among the most extensively studied in the world, but the current knowledge base is fragmentary, with taxonomic, ecological and genetic information scattered across different resources. Here we present the first comprehensive data repository of native and alien species optimized for fast and easy online access for ecological, evolutionary and conservation analyses. The inventory is based on the most recent reference flora of Britain and Ireland, with taxon names linked to unique Kew taxon identifiers and DNA barcode data. Our data resource for 3,227 species and 26 traits includes existing and unpublished genome sizes, chromosome numbers and life strategy and life-form assessments, along with existing data on functional traits, species distribution metrics, hybrid propensity, associated biomes, realized niche description, native status and geographic origin of alien species. This resource will facilitate both fundamental and applied research and enhance our understanding of the flora’s composition and temporal changes to inform conservation efforts in the face of ongoing climate change and biodiversity loss.
Influence of diurnal phase on behavioral tests of sensorimotor performance, anxiety, learning and memory in mice
Authors: Tsao Chi-Hui , Flint Jonathan , Huang Guo-Jen
Published: January 2022

Behavioral measurements in mice are critical tools used to evaluate the effects of interventions. Whilst mice are nocturnal animals, many studies conduct behavioral tests during the day. To better understand the effects of diurnal rhythm on mouse behaviors, we compared the results from behavioral tests conducted in the active and inactive phases. C57BL/6 mice were used in this study; we focus on sensorimotor performance, anxiety, learning and memory. Overall, our results show mice exhibit slightly higher cutaneous sensitivity, better long-term contextual memory, and a greater active avoidance escape response during the active phase. We did not observe significant differences in motor coordination, anxiety, or spatial learning and memory. Furthermore, apart from the elevated-O-maze, there was no remarkable sex effect among these tests. This study provides information on the effects of different diurnal phases on types of behavior and demonstrates the importance of the circadian cycle on learning and memory. Although we did not detect differences in anxiety and spatial learning/memory, diurnal rhythm may interact with other factors to influence these behaviors.
Protein interaction networks define the genetic architecture of preterm birth
Authors: Uzun Alper , Schuster Jessica S. , Stabila Joan , Zarate Valeria , Tollefson George A. , Agudelo Anthony , Kothiyal Prachi , Wong Wendy S. W. , Padbury James
Published: January 2022

The likely genetic architecture of complex diseases is that subgroups of patients share variants in genes in specific networks sufficient to express a shared phenotype. We combined high throughput sequencing with advanced bioinformatic approaches to identify such subgroups of patients with variants in shared networks. We performed targeted sequencing of patients with 2 or 3 generations of preterm birth on genes, gene sets and haplotype blocks that were highly associated with preterm birth. We analyzed the data using a multi-sample, protein–protein interaction (PPI) tool to identify significant clusters of patients associated with preterm birth. We identified shared protein interaction networks among preterm cases in two statistically significant clusters, p < 0.001. We also found two small control-dominated clusters. We replicated these data on an independent, large birth cohort. Separation testing showed significant similarity scores between the clusters from the two independent cohorts of patients. Canonical pathway analysis of the unique genes defining these clusters demonstrated enrichment in inflammatory signaling pathways, the glucocorticoid receptor, the insulin receptor, EGF and B-cell signaling, These results support a genetic architecture defined by subgroups of patients that share variants in genes in specific networks and pathways which are sufficient to give rise to the disease phenotype.
A new severity classification of lower limb secondary lymphedema based on lymphatic pathway defects in an indocyanine green fluorescent lymphography study
Authors: Shinaoka Akira , Kamiyama Kazuyo , Yamada Kiyoshi , Kimata Yoshihiro
Published: January 2022

Most protocols for lymphatic imaging of the lower limb conventionally inject tracer materials only into the interdigital space; however, recent studies indicate that there are four independent lymphatic vessel groups (anteromedial, anterolateral, posteromedial, and posterolateral) in the lower limb. Thus, three additional injection sites are needed for lymphatic imaging of the entire lower limb. We aimed to validate a multiple injection designed protocol and demonstrate its clinical benefits. Overall, 206 lower limbs undergoing indocyanine green fluorescent lymphography with the new injection protocol were registered retrospectively. To assess the influence of predictor variables on the degree of severity, multivariable logistic regression models were used with individual known risk factors. Using a generalized linear model, the area under the curve (AUC) of the conventional clinical model, comprising known severity risk factors, was compared with that of the modified model that included defects in the posterolateral and posteromedial groups. Multivariable logistic regression models showed a significant difference for the posteromedial and posterolateral groups. The AUC of the modified model was significantly improved compared to that of the conventional clinical model. Finding defects in the posteromedial and posterolateral groups is a significant criterion for judging lymphedema severity and introducing a new lymphedema severity classification.
Reduced calorie diet combined with NNMT inhibition establishes a distinct microbiome in DIO mice
Authors: Dimet-Wiley Andrea , Wu Qinglong , Wiley Jerrin T. , Eswar Aditya , Neelakantan Harshini , Savidge Tor , Watowich Stan
Published: January 2022

Treatment with a nicotinamide N-methyltransferase inhibitor (NNMTi; 5-amino-1-methylquinolinium) combined with low-fat diet (LD) promoted dramatic whole-body adiposity and weight loss in diet-induced obese (DIO) mice, rapidly normalizing these measures to age-matched lean animals, while LD switch alone was unable to restore these measures to age-matched controls in the same time frame. Since mouse microbiome profiles often highly correlate with body weight and fat composition, this study was designed to test whether the cecal microbiomes of DIO mice treated with NNMTi and LD were comparable to the microbiomes of age-matched lean counterparts and distinct from microbiomes of DIO mice maintained on a high-fat Western diet (WD) or subjected to LD switch alone. There were minimal microbiome differences between lean and obese controls, suggesting that diet composition and adiposity had limited effects. However, DIO mice switched from an obesity-promoting WD to an LD (regardless of treatment status) displayed several genera and phyla differences compared to obese and lean controls. While alpha diversity measures did not significantly differ between groups, beta diversity principal coordinates analyses suggested that mice from the same treatment group were the most similar. K-means clustering analysis of amplicon sequence variants by animal demonstrated that NNMTi-treated DIO mice switched to LD had a distinct microbiome pattern that was highlighted by decreased Erysipelatoclostridium and increased Lactobacillus relative abundances compared to vehicle counterparts; these genera are tied to body weight and metabolic regulation. Additionally, Parasutterella relative abundance, which was increased in both the vehicle- and NNMTi-treated LD-switched groups relative to the controls, significantly correlated with several adipose tissue metabolites’ abundances. Collectively, these results provide a novel foundation for future investigations.
Endothelial cells are an important source of BDNF in rat skeletal muscle
Authors: Cefis Marina , Chaney Remi , Quirié Aurore , Santini Clélia , Marie Christine , Garnier Philippe , Prigent-Tessier Anne
Published: January 2022

BDNF (brain-derived neurotrophic factor) is present in skeletal muscle, controlling muscular metabolism, strength and regeneration processes. However, there is no consensus on BDNF cellular source. Furthermore, while endothelial tissue expresses BDNF in large amount, whether endothelial cells inside muscle expressed BDNF has never been explored. The aim of the present study was to provide a comprehensive analysis of BDNF localization in rat skeletal muscle. Cellular localization of BDNF and activated Tropomyosin-related kinase B (TrkB) receptors was studied by immunohistochemical analysis on soleus (SOL) and gastrocnemius (GAS). BDNF and activated TrkB levels were also measured in muscle homogenates using Western blot analysis and/or Elisa tests. The results revealed BDNF immunostaining in all cell types examined with a prominent staining in endothelial cells and a stronger staining in type II than type I muscular fibers. Endothelial cells but not other cells displayed easily detectable activated TrkB receptor expression. Levels of BDNF and activated TrkB receptors were higher in SOL than GAS. In conclusion, endothelial cells are an important and still unexplored source of BDNF present in skeletal muscle. Endothelial BDNF expression likely explains why oxidative muscle exhibits higher BDNF levels than glycolytic muscle despite higher the BDNF expression by type II fibers.
Rapid syndromic PCR testing in patients with respiratory tract infections reduces time to results and improves microbial yield
Authors: Serigstad S. , Markussen D. , Grewal H. M. S. , Ebbesen M. , Kommedal Ø. , Heggelund L. , van Werkhoven C. H. , Faurholt-Jepsen D. , Clark T. W. , Ritz C. , Ulvestad E. , Bjørneklett R. , Knoop S. T. ,   The CAPNOR Study Group, Bjørneklett R. , Clark T. W. , Ebbesen M. , Faurholt-Jepsen D. , Grewal H. M. S. , Heggelund L. , Knoop S. T. , Kommedal Ø. , Markussen D. , Ravn P. , Ritz C. , Serigstad S. , Ulvestad E. , van Werkhoven C. H.
Published: January 2022

Lack of rapid and comprehensive microbiological diagnosis in patients with community acquired pneumonia (CAP) hampers appropriate antimicrobial therapy. This study evaluates the real-world performance of the BioFire FilmArray Pneumonia panel plus (FAP plus) and explores the feasibility of evaluation in a randomised controlled trial. Patients presenting to hospital with suspected CAP were recruited in a prospective feasibility study. An induced sputum or an endotracheal aspirate was obtained from all participants. The FAP plus turnaround time (TAT) and microbiological yield were compared with standard diagnostic methods (SDs). 96/104 (92%) enrolled patients had a respiratory tract infection (RTI); 72 CAP and 24 other RTIs. Median TAT was shorter for the FAP plus, compared with in-house PCR (2.6 vs 24.1 h, p < 0.001) and sputum cultures (2.6 vs 57.5 h, p < 0.001). The total microbiological yield by the FAP plus was higher compared to SDs (91% (162/179) vs 55% (99/179), p < 0.0001). Haemophilus influenzae, Streptococcus pneumoniae and influenza A virus were the most frequent pathogens. In conclusion, molecular panel testing in adults with CAP was associated with a significant reduction in time to actionable results and increased microbiological yield. The impact on antibiotic use and patient outcome should be assessed in randomised controlled trials.
GPR120 prevents colorectal adenocarcinoma progression by sustaining the mucosal barrier integrity
Authors: Rubbino Federica , Garlatti Valentina , Garzarelli Valeria , Massimino Luca , Spanò Salvatore , Iadarola Paolo , Cagnone Maddalena , Giera Martin , Heijink Marieke , Guglielmetti Simone , Arena Vincenzo , Malesci Alberto , Laghi Luigi , Danese Silvio , Vetrano Stefania
Published: January 2022

GPR120 (encoded by FFAR4 gene) is a receptor for long chain fatty acids, activated by ω-3 Polyunsaturated Fatty Acids (PUFAs), and expressed in many cell types. Its role in the context of colorectal cancer (CRC) is still puzzling with many controversial evidences. Here, we explored the involvement of epithelial GPR120 in the CRC development. Both in vitro and in vivo experiments were conducted to mimic the conditional deletion of the receptor from gut epithelium. Intestinal permeability and integrity of mucus layer were assessed by using Evans blue dye and immunofluorescence for MUC-2 protein, respectively. Microbiota composition, presence of lipid mediators and short chain fatty acids were analyzed in the stools of conditional GPR120 and wild type (WT) mice. Incidence and grade of tumors were evaluated in all groups of mice before and after colitis-associated cancer. Finally, GPR120 expression was analyzed in 9 human normal tissues, 9 adenomas, and 17 primary adenocarcinomas. Our work for the first time highlights the role of the receptor in the progression of colorectal cancer. We observed that the loss of epithelial GPR120 in the gut results into increased intestinal permeability, microbiota translocation and dysbiosis, which turns into hyperproliferation of epithelial cells, likely through the activation of β -catenin signaling. Therefore, the loss of GPR120 represents an early event of CRC, but avoid its progression as invasive cancer. these results demonstrate that the epithelial GPR120 receptor is essential to maintain the mucosal barrier integrity and to prevent CRC developing. Therefore, our data pave the way to GPR120 as an useful marker for the phenotypic characterization of CRC lesions and as new potential target for CRC prevention.
Magnetoencephalography resting-state correlates of executive and language components of verbal fluency
Authors: Oswald Victor , Zerouali Younes , Boulet-Craig Aubrée , Krajinovic Maja , Laverdière Caroline , Sinnett Daniel , Jolicoeur Pierre , Lippé Sarah , Jerbi Karim , Robaey Philippe
Published: January 2022

Verbal fluency (VF) is a heterogeneous cognitive function that requires executive as well as language abilities. The purpose of this study was to elucidate the specificity of the resting state MEG correlates of the executive and language components. To this end, we administered a VF test, another verbal test (Vocabulary), and another executive test (Trail Making Test), and we recorded 5-min eyes-open resting-state MEG data in 28 healthy participants. We used source-reconstructed spectral power estimates to compute correlation/anticorrelation MEG clusters with the performance at each test, as well as with the advantage in performance between tests, across individuals using cluster-level statistics in the standard frequency bands. By obtaining conjunction clusters between verbal fluency scores and factor loading obtained for verbal fluency and each of the two other tests, we showed a core of slow clusters (delta to beta) localized in the right hemisphere, in adjacent parts of the premotor, pre-central and post-central cortex in the mid-lateral regions related to executive monitoring. We also found slow parietal clusters bilaterally and a cluster in the gamma 2 and 3 bands in the left inferior frontal gyrus likely associated with phonological processing involved in verbal fluency.
Assessing the impact of human mobility to predict regional excess death in Ecuador
Authors: Cuéllar Leticia , Torres Irene , Romero-Severson Ethan , Mahesh Riya , Ortega Nathaniel , Pungitore Sarah , Ke Ruian , Hengartner Nicolas
Published: January 2022

COVID-19 outbreaks have had high mortality in low- and middle-income countries such as Ecuador. Human mobility is an important factor influencing the spread of diseases possibly leading to a high burden of disease at the country level. Drastic control measures, such as complete lockdown, are effective epidemic controls, yet in practice one hopes that a partial shutdown would suffice. It is an open problem to determine how much mobility can be allowed while controlling an outbreak. In this paper, we use statistical models to relate human mobility to the excess death in Ecuador while controlling for demographic factors. The mobility index provided by GRANDATA, based on mobile phone users, represents the change of number of out-of-home events with respect to a benchmark date (March 2nd, 2020). The study confirms the global trend that more men are dying than expected compared to women, and that people under 30 show less deaths than expected, particularly individuals younger than 20 with a death rate reduction between 22 and 27%. The weekly median mobility time series shows a sharp decrease in human mobility immediately after a national lockdown was declared on March 17, 2020 and a progressive increase towards the pre-lockdown level within two months. Relating median mobility to excess deaths shows a lag in its effect: first, a decrease in mobility in the previous two to three weeks decreases excess death and, more novel, we found an increase of mobility variability four weeks prior increases the number of excess deaths.
Deep robust residual network for super-resolution of 2D fetal brain MRI
Authors: Song Liyao , Wang Quan , Liu Ting , Li Haiwei , Fan Jiancun , Yang Jian , Hu Bingliang
Published: January 2022

Spatial resolution is a key factor of quantitatively evaluating the quality of magnetic resonance imagery (MRI). Super-resolution (SR) approaches can improve its spatial resolution by reconstructing high-resolution (HR) images from low-resolution (LR) ones to meet clinical and scientific requirements. To increase the quality of brain MRI, we study a robust residual-learning SR network (RRLSRN) to generate a sharp HR brain image from an LR input. Due to the Charbonnier loss can handle outliers well, and Gradient Difference Loss (GDL) can sharpen an image, we combined the Charbonnier loss and GDL to improve the robustness of the model and enhance the texture information of SR results. Two MRI datasets of adult brain, Kirby 21 and NAMIC, were used to train and verify the effectiveness of our model. To further verify the generalizability and robustness of the proposed model, we collected eight clinical fetal brain MRI 2D data for evaluation. The experimental results have shown that the proposed deep residual-learning network achieved superior performance and high efficiency over other compared methods.
Psychological factors underpinning vaccine willingness in Israel, Japan and Hungary
Authors: Goodwin Robin , Ben-Ezra Menachem , Takahashi Masahito , Luu Lan-Anh Nguyen , Borsfay Krisztina , Kovács Mónika , Hou Wai Kai , Hamama-Raz Yaira , Levin Yafit
Published: January 2022

The spread of SARS-CoV-2 led to rapid vaccine development. However, there remains considerable vaccine hesitancy in some countries. We investigate vaccine willingness in three nations with very different vaccine histories: Israel, Japan and Hungary. Employing an ecological-systems approach we analyse associations between health status, individual cognitions, norms, trust in government, COVID-19 myths and willingness to be vaccinated, with data from three nationally representative samples (Israel, Jan. 2021, N = 1011; Japan, Feb. 2021, N = 997; Hungary, April 2021, N = 1130). Vaccine willingness was higher in Israel (74%) than Japan (51%) or Hungary (31%). In all three countries vaccine willingness was greatest amongst who would regret not being vaccinated and respondents who trusted their government. Multi-group latent class analysis identified three groups of COVID myths, with particular concern about alteration of DNA (Israel), allergies (Hungary) and infection from the vaccine (Japan). Intervention campaigns should address such cultural myths while emphasising both individual and social benefits of vaccination.