bluuebunny/crossref_metadata_2025 huggingface dataset:
Continental Reworking in the Eastern South China Block and Its Adjacent Areas Revealed by F‐J Multimodal Ambient Noise Tomography
Authors: Chen Juqing , Pan Lei , Li Zhengbo , Chen Xiaofei
Published: October 2022

The eastern South China Block (SCB) has experienced complex and drastic reworking processes since the early Neoproterozoic, the mechanisms of which remain unclear. To better understand the continental reworking mechanisms in the eastern SCB, we imaged the shear‐wave velocity structure of the crust and upper mantle in the eastern SCB and its adjacent areas with the F‐J multimodal ambient noise tomography method. The seismic ambient noise data were acquired by 652 seismic stations in this area. The shear‐wave velocity model presents widespread mid‐crustal low‐velocity zones (MCLVZs) and upper mantle low‐velocity zones (UMLVZs), the distribution of which shows a good correlation with regional tectonics. The MCLVZs formed due to compositional and structural layering during the late Neoproterozoic to the early Phanerozoic. The disrupted MCLVZs near the Qinling‐Dabie orogen can be linked to metamorphism caused by a continental collision between the SCB and the North China Craton during the Triassic Indosinian event. The thin crustal and lithospheric thicknesses east of the North‐South Gravity Lineament may be the result of asthenospheric upwelling due to the subduction of the Pacific plate since the late Mesozoic. In the areas near the Shaoxing‐Jiangshan‐Pingxiang fault zone and the Tanlu fault zone, upheaval UMLVZs indicate that these ancient fault zones were reactivated by the subduction of the Pacific plate, providing channels for asthenospheric upwelling. Well‐preserved MCLVZs north of the Qinling‐Dabie orogen can be used to assess compressions and extensions induced by the subduction of the Pacific plate.
Metabolic guidance and stress in tumors modulate antigen-presenting cells
Authors: Park Jaeoh , Wang Limei , Ho Ping-Chih
Published: October 2022

Successful antitumor immunity largely relies on efficient T cell priming by antigen-presenting cells (APCs); however, the capacity of APCs is found to be defective in many cancers. Metabolically reprogrammed cancer cells support the energetic and biosynthetic demands of their high proliferation rates by exploiting nutrients available in the tumor microenvironment (TME), which in turn limits proper metabolic reprogramming of APCs during recruitment, differentiation, activation and antigen presentation. Furthermore, some metabolites generated by the TME are unfavorable to antitumor immunity. This review summarizes recent studies on the metabolic features of APCs and their functionality in the TME. Particularly, we will describe how APCs respond to altered TME and how metabolic byproducts from cancer and immunomodulatory cells affect APCs. Finally, we introduce the current status of APC-oriented research and clinical trials targeting metabolic features to boost efficient immunotherapy.
Enhanced radiation-induced immunogenic cell death activates chimeric antigen receptor T cells by targeting CD39 against glioblastoma
Authors: Sun Ting , Li Yanyan , Yang Ying , Liu Bin , Cao Yufei , Yang Wei
Published: October 2022

Chimeric antigen receptor (CAR)-T cells directed to solid tumors have been less effective, due in part to the low or lost expression of specific tumor antigens. Herein, we developed a different strategy to enhance CAR-T cell persistence and efficacy by producing a multispecific CAR-T or vaccine based on immunogenic cell death (ICD). We demonstrated that ionizing radiation activates STAT1-IRF1-CD39 axis to upregulate CD39 expression to form an immunosuppressive tumor microenvironment (TME) to enhance radioresistance. CD39 blockade accumulates extracellular ATP, which activates NLRP3 inflammasome in dendritic cells via P2X7 receptor, thereby promoting radiation-induced ICD. Multispecific CAR-T cells in vitro prepared by elevated ICD suppress the growth of xenografts in nude mice. Radiation and CD39 inhibition-induced ICD of glioma stem cells as a vaccine enhance CAR-T expansion in peripheral blood, multifunctionality in the TME, and antitumor effect in a glioma model. The multispecificity of CAR-T cells, targeting CAR and tumor antigens, vastly enhances the function of conventional CAR-T cells, stimulates a native immune response, and overcomes obstacles of specific antigen loss or low expression of target cells in antitumor therapy.
The role of cancer-associated fibroblasts in tumorigenesis of gastric cancer
Authors: Sun Hui , Wang Xu , Wang Xin , Xu Midie , Sheng Weiqi
Published: October 2022

Despite advances in anticancer therapy, the prognosis of gastric cancer (GC) remains unsatisfactory. Research in recent years has shown that the malignant behavior of cancer is not only attributable to tumor cells but is partly mediated by the activity of the cancer stroma and controlled by various molecular networks in the tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) are one of the most abundant mesenchymal cell components of the stroma and extensively participate in the malignant development of GC malignancy. CAFs modulate the biological properties of tumor cells in multiple ways, including the secretion of various bioactive molecules that have effects through paracrine and autocrine signaling, the release of exosomes, and direct interactions, thereby affecting GC initiation and development. However, there is marked heterogeneity in the cellular origins, phenotypes, and functions of CAFs in the TME of GC. Furthermore, variations in factors, such as proteins, microRNAs, and lncRNAs, affect interactions between CAFs and GC cells, although, the potential molecular mechanisms are still poorly understood. In this review, we aim to describe the current knowledge of the cellular features and heterogeneity of CAFs and discuss how these factors are regulated in CAFs, with a focus on how they affect GC biology. This review provides mechanistic insight that could inform therapeutic strategies and improve the prognosis of GC patients.
Periodic structural changes in Pd nanoparticles during oscillatory CO oxidation reaction
Authors: Ghosh Tanmay , Arce-Ramos Juan Manuel , Li Wen-Qing , Yan Hongwei , Chee See Wee , Genest Alexander , Mirsaidov Utkur
Published: October 2022

Nanoparticle (NP) catalysts are ubiquitous in energy systems, chemical production, and reducing the environmental impact of many industrial processes. Under reactive environments, the availability of catalytically active sites on the NP surface is determined by its dynamic structure. However, atomic-scale insights into how a NP surface reconstructs under reaction conditions and the impact of the reconstruction on catalytic activity are still lacking. Using operando transmission electron microscopy, we show that Pd NPs exhibit periodic round–to–flat transitions altering their facets during CO oxidation reaction at atmospheric pressure and elevated temperatures. This restructuring causes spontaneous oscillations in the conversion of CO to CO2 under constant reaction conditions. Our study reveals that the oscillatory behavior stems from the CO-adsorption-mediated periodic restructuring of the nanocatalysts between high-index-faceted round and low-index-faceted flat shapes. These atomic-scale insights into the dynamic surface properties of NPs under reactive conditions play an important role in the design of high-performance catalysts.
Stabilization of three-dimensional charge order through interplanar orbital hybridization in PrxY1−xBa2Cu3O6+δ
Authors: Ruiz Alejandro , Gunn Brandon , Lu Yi , Sasmal Kalyan , Moir Camilla M. , Basak Rourav , Huang Hai , Lee Jun-Sik , Rodolakis Fanny , Boyle Timothy J. , Walker Morgan , He Yu , Blanco-Canosa Santiago , da Silva Neto Eduardo H. , Maple M. Brian , Frano Alex
Published: October 2022

The shape of 3d-orbitals often governs the electronic and magnetic properties of correlated transition metal oxides. In the superconducting cuprates, the planar confinement of the $${d}_{{x}^{2}-{y}^{2}}$$

d

x

2

−

y

2

orbital dictates the two-dimensional nature of the unconventional superconductivity and a competing charge order. Achieving orbital-specific control of the electronic structure to allow coupling pathways across adjacent planes would enable direct assessment of the role of dimensionality in the intertwined orders. Using Cu L3 and Pr M5 resonant x-ray scattering and first-principles calculations, we report a highly correlated three-dimensional charge order in Pr-substituted YBa2Cu3O7, where the Pr f-electrons create a direct orbital bridge between CuO2 planes. With this we demonstrate that interplanar orbital engineering can be used to surgically control electronic phases in correlated oxides and other layered materials.
Molecular architecture of the glycogen- committed PP1/PTG holoenzyme
Authors: Semrau Marta Stefania , Giachin Gabriele , Covaceuszach Sonia , Cassetta Alberto , Demitri Nicola , Storici Paola , Lolli Graziano
Published: October 2022

The delicate alternation between glycogen synthesis and degradation is governed by the interplay between key regulatory enzymes altering the activity of glycogen synthase and phosphorylase. Among these, the PP1 phosphatase promotes glycogenesis while inhibiting glycogenolysis. PP1 is, however, a master regulator of a variety of cellular processes, being conveniently directed to each of them by scaffolding subunits. PTG, Protein Targeting to Glycogen, addresses PP1 action to glycogen granules. In Lafora disease, the most aggressive pediatric epilepsy, genetic alterations leading to PTG accumulation cause the deposition of insoluble polyglucosans in neurons. Here, we report the crystallographic structure of the ternary complex PP1/PTG/carbohydrate. We further refine the mechanism of the PTG-mediated PP1 recruitment to glycogen by identifying i) an unusual combination of recruitment sites, ii) their contributions to the overall binding affinity, and iii) the conformational heterogeneity of this complex by in solution SAXS analyses.
Controlled large non-reciprocal charge transport in an intrinsic magnetic topological insulator MnBi2Te4
Authors: Zhang Zhaowei , Wang Naizhou , Cao Ning , Wang Aifeng , Zhou Xiaoyuan , Watanabe Kenji , Taniguchi Takashi , Yan Binghai , Gao Wei-bo
Published: October 2022

Symmetries, quantum geometries and electronic correlations are among the most important ingredients of condensed matters, and lead to nontrivial phenomena in experiments, for example, non-reciprocal charge transport. Of particular interest is whether the non-reciprocal transport can be manipulated. Here, we report the controllable large non-reciprocal charge transport in the intrinsic magnetic topological insulator MnBi2Te4. The current direction relevant resistance is observed at chiral edges, which is magnetically switchable, edge position sensitive and stacking sequence controllable. Applying gate voltage can also effectively manipulate the non-reciprocal response. The observation and manipulation of non-reciprocal charge transport reveals the fundamental role of chirality in charge transport of MnBi2Te4, and pave ways to develop van der Waals spintronic devices by chirality engineering.
The genome and lifestage-specific transcriptomes of a plant-parasitic nematode and its host reveal susceptibility genes involved in trans-kingdom synthesis of vitamin B5
Authors: Siddique Shahid , Radakovic Zoran S. , Hiltl Clarissa , Pellegrin Clement , Baum Thomas J. , Beasley Helen , Bent Andrew F. , Chitambo Oliver , Chopra Divykriti , Danchin Etienne G. J. , Grenier Eric , Habash Samer S. , Hasan M. Shamim , Helder Johannes , Hewezi Tarek , Holbein Julia , Holterman Martijn , Janakowski Sławomir , Koutsovoulos Georgios D. , Kranse Olaf P. , Lozano-Torres Jose L. , Maier Tom R. , Masonbrink Rick E. , Mendy Badou , Riemer Esther , Sobczak Mirosław , Sonawala Unnati , Sterken Mark G. , Thorpe Peter , van Steenbrugge Joris J. M. , Zahid Nageena , Grundler Florian , Eves-van den Akker Sebastian
Published: October 2022

Plant-parasitic nematodes are a major threat to crop production in all agricultural systems. The scarcity of classical resistance genes highlights a pressing need to find new ways to develop nematode-resistant germplasm. Here, we sequence and assemble a high-quality phased genome of the model cyst nematode Heterodera schachtii to provide a platform for the first system-wide dual analysis of host and parasite gene expression over time, covering all major parasitism stages. Analysis of the hologenome of the plant-nematode infection site identified metabolic pathways that were incomplete in the parasite but complemented by the host. Using a combination of bioinformatic, genetic, and biochemical approaches, we show that a highly atypical completion of vitamin B5 biosynthesis by the parasitic animal, putatively enabled by a horizontal gene transfer from a bacterium, is required for full pathogenicity. Knockout of either plant-encoded or now nematode-encoded steps in the pathway significantly reduces parasitic success. Our experiments establish a reference for cyst nematodes, further our understanding of the evolution of plant-parasitism by nematodes, and show that congruent differential expression of metabolic pathways in the infection hologenome represents a new way to find nematode susceptibility genes. The approach identifies genome-editing-amenable targets for future development of nematode-resistant crops.
Coupling photocatalytic water oxidation with reductive transformations of organic molecules
Authors: Tian Xinzhe , Guo Yinggang , An Wankai , Ren Yun-Lai , Qin Yuchen , Niu Caoyuan , Zheng Xin
Published: October 2022

The utilization of readily available and non-toxic water by photocatalytic water splitting is highly attractive in green chemistry. Herein we report that light-induced oxidative half-reaction of water splitting is effectively coupled with reduction of organic compounds, which provides a light-induced avenue to use water as an electron donor to enable reductive transformations of organic substances. The present strategy allows various aryl bromides to undergo smoothly the reductive coupling with Pd/g-C3N4* as the photocatalyst, giving a pollutive reductant-free method for synthesizing biaryl skeletons. Moreover, the use of green visible-light energy endows this process with more advantages including mild conditions and good functional group tolerance. Although this method has some disadvantages such as a use of environmentally unfriendly 1,2-dioxane, an addition of Na2CO3 and so on, it can guide chemists to use water as a reducing agent to develop clean procedures for various organic reactions.
HBEGF-TNF induce a complex outer retinal pathology with photoreceptor cell extrusion in human organoids
Authors: Völkner Manuela , Wagner Felix , Steinheuer Lisa Maria , Carido Madalena , Kurth Thomas , Yazbeck Ali , Schor Jana , Wieneke Stephanie , Ebner Lynn J. A. , Del Toro Runzer Claudia , Taborsky David , Zoschke Katja , Vogt Marlen , Canzler Sebastian , Hermann Andreas , Khattak Shahryar , Hackermüller Jörg , Karl Mike O.
Published: October 2022

Human organoids could facilitate research of complex and currently incurable neuropathologies, such as age-related macular degeneration (AMD) which causes blindness. Here, we establish a human retinal organoid system reproducing several parameters of the human retina, including some within the macula, to model a complex combination of photoreceptor and glial pathologies. We show that combined application of TNF and HBEGF, factors associated with neuropathologies, is sufficient to induce photoreceptor degeneration, glial pathologies, dyslamination, and scar formation: These develop simultaneously and progressively as one complex phenotype. Histologic, transcriptome, live-imaging, and mechanistic studies reveal a previously unknown pathomechanism: Photoreceptor neurodegeneration via cell extrusion. This could be relevant for aging, AMD, and some inherited diseases. Pharmacological inhibitors of the mechanosensor PIEZO1, MAPK, and actomyosin each avert pathogenesis; a PIEZO1 activator induces photoreceptor extrusion. Our model offers mechanistic insights, hypotheses for neuropathologies, and it could be used to develop therapies to prevent vision loss or to regenerate the retina in patients suffering from AMD and other diseases.
The metabolic effects of adding exenatide to basal insulin therapy when targeting remission in early type 2 diabetes in a randomized clinical trial
Authors: Retnakaran Ravi , Ye Chang , Emery Alexandra , Kramer Caroline K. , Zinman Bernard
Published: October 2022

Combining a glucagon-like peptide-1 receptor agonist (GLP1-RA) with basal insulin is an emerging option when initiating injectable therapy in longstanding type 2 diabetes (T2DM). Recognizing that short-term insulin therapy can improve beta-cell function and induce glycemic remission in early T2DM, we hypothesized that adding the short-acting GLP1-RA exenatide to basal insulin in early T2DM may enhance the achievability of these outcomes. In this completed, 20-week, open-label, parallel-arm trial at an academic hospital, 103 individuals aged 30–80 years with <7 years duration of T2DM were randomized (by computer-generated sequence) to 8-weeks treatment with (i) insulin glargine (Glar; n = 33), (ii) glargine + thrice-daily lispro (Glar/Lispro; n = 35), or (iii) glargine + twice-daily exenatide (Glar/Exenatide; n = 35), followed by 12-weeks washout. The analyzed population of 102 participants (median 3.5 years of T2DM, A1c 6.6% ±0.7%) consisted of 33 on Glar, 35 on Glar/Lispro and 34 on Glar/Exenatide. Oral glucose tolerance tests at baseline, 4-weeks, 8-weeks and 20-weeks enabled assessment of beta-cell function (Insulin Secretion-Sensitivity Index-2 (ISSI-2)) and glycemic control. Mean ISSI-2 over the 8-week intervention (primary outcome) did not differ across the groups (Glar/Exenatide 237 ± 11; Glar/Lispro 208 ± 11; Glar 223 ± 11; p = 0.19). Baseline-adjusted A1c at 8-weeks (secondary outcome) was lowest in Glar/Exenatide followed by Glar/Lispro and Glar (mean 5.9% vs 6.0% vs 6.2%; p = 0.0007). After 12-weeks washout, however, neither baseline-adjusted A1c nor baseline-adjusted ISSI-2 (secondary outcomes) differed between the groups, nor did (additional outcome) rates of remission (Glar/Exenatide 26.7%, Glar/Lispro 43.8%, Glar 32.1%; p = 0.35). There were no severe hypoglycemia episodes. In conclusion, adding exenatide to basal insulin in early T2DM does not further enhance underlying beta-cell function or the capacity to achieve diabetes remission, despite yielding on-treatment glycemic benefit.
Host genetic factors related to innate immunity, environmental sensing and cellular functions are associated with human skin microbiota
Authors: Moitinho-Silva Lucas , Degenhardt Frauke , Rodriguez Elke , Emmert Hila , Juzenas Simonas , Möbus Lena , Uellendahl-Werth Florian , Sander Nicole , Baurecht Hansjörg , Tittmann Lukas , Lieb Wolfgang , Gieger Christian , Peters Annette , Ellinghaus David , Bang Corinna , Franke Andre , Weidinger Stephan , Rühlemann Malte Christoph
Published: October 2022

Despite the increasing knowledge about factors shaping the human microbiome, the host genetic factors that modulate the skin-microbiome interactions are still largely understudied. This contrasts with recent efforts to characterize host genes that influence the gut microbiota. Here, we investigated the effect of genetics on skin microbiota across three different skin microenvironments through meta-analyses of genome-wide association studies (GWAS) of two population-based German cohorts. We identified 23 genome-wide significant loci harboring 30 candidate genes involved in innate immune signaling, environmental sensing, cell differentiation, proliferation and fibroblast activity. However, no locus passed the strict threshold for study-wide significance (P < 6.3 × 10−10for 80 features included in the analysis). Mendelian randomization (MR) analysis indicated the influence of staphylococci on eczema/dermatitis and suggested modulating effects of the microbiota on other skin diseases. Finally, transcriptional profiles of keratinocytes significantly changed after in vitro co-culturing withStaphylococcus epidermidis, chosen as a representative of skin commensals. Seven candidate genes from the GWAS were found overlapping with differential expression in the co-culturing experiments, warranting further research of the skin commensal and host genetic makeup interaction.
Search for Dark Matter Axions with CAST-CAPP
Authors: Adair C. M. , Altenmüller K. , Anastassopoulos V. , Arguedas Cuendis S. , Baier J. , Barth K. , Belov A. , Bozicevic D. , Bräuninger H. , Cantatore G. , Caspers F. , Castel J. F. , Çetin S. A. , Chung W. , Choi H. , Choi J. , Dafni T. , Davenport M. , Dermenev A. , Desch K. , Döbrich B. , Fischer H. , Funk W. , Galan J. , Gardikiotis A. , Gninenko S. , Golm J. , Hasinoff M. D. , Hoffmann D. H. H. , Díez Ibáñez D. , Irastorza I. G. , Jakovčić K. , Kaminski J. , Karuza M. , Krieger C. , Kutlu Ç. , Lakić B. , Laurent J. M. , Lee J. , Lee S. , Luzón G. , Malbrunot C. , Margalejo C. , Maroudas M. , Miceli L. , Mirallas H. , Obis L. , Özbey A. , Özbozduman K. , Pivovaroff M. J. , Rosu M. , Ruz J. , Ruiz-Chóliz E. , Schmidt S. , Schumann M. , Semertzidis Y. K. , Solanki S. K. , Stewart L. , Tsagris I. , Vafeiadis T. , Vogel J. K. , Vretenar M. , Youn S. , Zioutas K.
Published: October 2022

The CAST-CAPP axion haloscope, operating at CERN inside the CAST dipole magnet, has searched for axions in the 19.74 μeV to 22.47 μeV mass range. The detection concept follows the Sikivie haloscope principle, where Dark Matter axions convert into photons within a resonator immersed in a magnetic field. The CAST-CAPP resonator is an array of four individual rectangular cavities inserted in a strong dipole magnet, phase-matched to maximize the detection sensitivity. Here we report on the data acquired for 4124 h from 2019 to 2021. Each cavity is equipped with a fast frequency tuning mechanism of 10 MHz/ min between 4.774 GHz and 5.434 GHz. In the present work, we exclude axion-photon couplings for virialized galactic axions down to gaγγ = 8 × 10−14 GeV−1 at the 90% confidence level. The here implemented phase-matching technique also allows for future large-scale upgrades.
P300 promotes tumor recurrence by regulating radiation-induced conversion of glioma stem cells to vascular-like cells
Authors: Muthukrishnan Sree Deepthi , Kawaguchi Riki , Nair Pooja , Prasad Rachna , Qin Yue , Johnson Maverick , Wang Qing , VanderVeer-Harris Nathan , Pham Amy , Alvarado Alvaro G. , Condro Michael C. , Gao Fuying , Gau Raymond , Castro Maria G. , Lowenstein Pedro R. , Deb Arjun , Hinman Jason D. , Pajonk Frank , Burns Terry C. , Goldman Steven A. , Geschwind Daniel H. , Kornblum Harley I.
Published: October 2022

Glioma stem cells (GSC) exhibit plasticity in response to environmental and therapeutic stress leading to tumor recurrence, but the underlying mechanisms remain largely unknown. Here, we employ single-cell and whole transcriptomic analyses to uncover that radiation induces a dynamic shift in functional states of glioma cells allowing for acquisition of vascular endothelial-like and pericyte-like cell phenotypes. These vascular-like cells provide trophic support to promote proliferation of tumor cells, and their selective depletion results in reduced tumor growth post-treatment in vivo. Mechanistically, the acquisition of vascular-like phenotype is driven by increased chromatin accessibility and H3K27 acetylation in specific vascular genes allowing for their increased expression post-treatment. Blocking P300 histone acetyltransferase activity reverses the epigenetic changes induced by radiation and inhibits the adaptive conversion of GSC into vascular-like cells and tumor growth. Our findings highlight a role for P300 in radiation-induced stress response, suggesting a therapeutic approach to prevent glioma recurrence.
Remodelling of tumour microenvironment by microwave ablation potentiates immunotherapy of AXL-specific CAR T cells against non-small cell lung cancer
Authors: Cao Bihui , Liu Manting , Wang Lu , Zhu Kangshun , Cai Mingyue , Chen Xiaopei , Feng Yunfei , Yang Shuo , Fu Shengyu , Zhi Cheng , Ye Xiaodie , Zhang Jian , Zhang Zhiru , Yang Xin , Zhao Ming , Wu Qingde , Xu Linfeng , Yang Lili , Lian Hui , Zhao Qi , Zhang Zhenfeng
Published: October 2022

The complex immunosuppressive tumour microenvironment (TME) and lack of tumour-specific targets hinder the application of chimeric antigen receptor (CAR) T cells in the treatment of solid tumours. Combining local treatment with CAR T cell immunotherapy may regulate the TME and enhance the killing potency of CAR T cells in solid tumours. Here, we show that AXL, which is highly expressed in non-small cell lung cancer (NSCLC) but not in normal tissues, might be a target for CAR T cell therapy. AXL-CAR T cells alone cause moderate tumour regression in subcutaneous and pulmonary metastatic lung cancer cell-derived xenograft models. Combination of microwave ablation (MWA) and AXL-CAR T cells have superior antitumour efficacy. MWA enhances the activation, infiltration, persistence and tumour suppressive properties of AXL-CAR T cells in AXL-positive NSCLC patient-derived xenograft tumours via TME remodelling. The combination therapy increases the mitochondrial oxidative metabolism of tumour-infiltrating CAR T cells. Combination treatment induces significant tumour suppression without observed toxicities in humanized immunocompetent mice. The synergistic therapeutic effect of MWA and AXL-CAR T cells may be valuable for NSCLC treatment.
Brainstem networks construct threat probability and prediction error from neuronal building blocks
Authors: Strickland Jasmin A. , McDannald Michael A.
Published: October 2022

When faced with potential threat we must estimate its probability, respond advantageously, and leverage experience to update future estimates. Threat estimation is the proposed domain of the forebrain, while behaviour is elicited by the brainstem. Yet, the brainstem is also a source of prediction error, a learning signal to acquire and update threat estimates. Neuropixels probes allowed us to record single-unit activity across a 21-region brainstem axis in rats receiving probabilistic fear discrimination with foot shock outcome. Against a backdrop of diffuse behaviour signaling, a brainstem network with a dorsal hub signaled threat probability. Neuronal function remapping during the outcome period gave rise to brainstem networks signaling prediction error and shock on multiple timescales. The results reveal brainstem networks construct threat probability, behaviour, and prediction error signals from neuronal building blocks.
Reduced alcohol preference and intake after fecal transplant in patients with alcohol use disorder is transmissible to germ-free mice
Authors: Wolstenholme Jennifer T. , Saunders Justin M. , Smith Maren , Kang Jason D. , Hylemon Phillip B. , González-Maeso Javier , Fagan Andrew , Zhao Derrick , Sikaroodi Masoumeh , Herzog Jeremy , Shamsaddini Amirhossein , Peña-Rodríguez Marcela , Su Lianyong , Tai Yun-Ling , Zheng Jing , Cheng Po-Cheng , Sartor R. Balfour , Gillevet Patrick M. , Zhou Huiping , Bajaj Jasmohan S.
Published: October 2022

Alcohol use disorder is a major cause of morbidity, which requires newer treatment approaches. We previously showed in a randomized clinical trial that alcohol craving and consumption reduces after fecal transplantation. Here, to determine if this could be transmitted through microbial transfer, germ-free male C57BL/6 mice received stool or sterile supernatants collected from the trial participants pre-/post-fecal transplant. We found that mice colonized with post-fecal transplant stool but not supernatants reduced ethanol acceptance, intake and preference versus pre-fecal transplant colonized mice. Microbial taxa that were higher in post-fecal transplant humans were also associated with lower murine alcohol intake and preference. A majority of the differentially expressed genes (immune response, inflammation, oxidative stress response, and epithelial cell proliferation) occurred in the intestine rather than the liver and prefrontal cortex. These findings suggest a potential for therapeutically targeting gut microbiota and the microbial-intestinal interface to alter gut-liver-brain axis and reduce alcohol consumption in humans.
ReSurveyGermany: Vegetation-plot time-series over the past hundred years in Germany
Authors: Jandt Ute , Bruelheide Helge , Berg Christian , Bernhardt-Römermann Markus , Blüml Volker , Bode Frank , Dengler Jürgen , Diekmann Martin , Dierschke Hartmut , Doerfler Inken , Döring Ute , Dullinger Stefan , Härdtle Werner , Haider Sylvia , Heinken Thilo , Horchler Peter , Jansen Florian , Kudernatsch Thomas , Kuhn Gisbert , Lindner Martin , Matesanz Silvia , Metze Katrin , Meyer Stefan , Müller Frank , Müller Norbert , Naaf Tobias , Peppler-Lisbach Cord , Poschlod Peter , Roscher Christiane , Rosenthal Gert , Rumpf Sabine B. , Schmidt Wolfgang , Schrautzer Joachim , Schwabe Angelika , Schwartze Peter , Sperle Thomas , Stanik Nils , Stroh Hans-Georg , Storm Christian , Voigt Winfried , von Heßberg Andreas , von Oheimb Goddert , Wagner Eva-Rosa , Wegener Uwe , Wesche Karsten , Wittig Burghard , Wulf Monika
Published: October 2022

Vegetation-plot resurvey data are a main source of information on terrestrial biodiversity change, with records reaching back more than one century. Although more and more data from re-sampled plots have been published, there is not yet a comprehensive open-access dataset available for analysis. Here, we compiled and harmonised vegetation-plot resurvey data from Germany covering almost 100 years. We show the distribution of the plot data in space, time and across habitat types of the European Nature Information System (EUNIS). In addition, we include metadata on geographic location, plot size and vegetation structure. The data allow temporal biodiversity change to be assessed at the community scale, reaching back further into the past than most comparable data yet available. They also enable tracking changes in the incidence and distribution of individual species across Germany. In summary, the data come at a level of detail that holds promise for broadening our understanding of the mechanisms and drivers behind plant diversity change over the last century.
Intrinsic connectivity within the affective salience network moderates adolescent susceptibility to negative and positive peer norms
Authors: Do Kathy T. , McCormick Ethan M. , Prinstein Mitchell J. , Lindquist Kristen A. , Telzer Eva H.
Published: October 2022

Not all adolescents are equally susceptible to peer influence, and for some, peer influence exerts positive rather than negative effects. Using resting-state functional magnetic resonance imaging, the current study examined how intrinsic functional connectivity networks associated with processing social cognitive and affective stimuli predict adolescents’ (n = 87, ages 11–14 years) prosocial tendencies and risky behaviors in the context of positive and negative peer norms. We tested the moderating role of four candidate intrinsic brain networks—associated with mentalizing, cognitive control, motivational relevance, and affective salience—in peer influence susceptibility. Only intrinsic connectivity within the affective salience network significantly moderated the association between peer norms and adolescent behavior above and beyond the other networks. Adolescents with high intrinsic connectivity within the affective salience network reported greater prosocial tendencies in contexts with more positive peer norms but greater risk-taking behavior in contexts with more negative peer norms. In contrast, peer norms were not associated with adolescent behavior for individuals with low affective salience within-network intrinsic connectivity. The mentalizing network, cognitive control network, and motivational relevance network were not associated with individual differences in peer influence susceptibility. This study identifies key neural mechanisms underlying differential susceptibility to positive and negative peer influence in early adolescence, with a particular emphasis on the role of affective salience over traditional mentalizing, regulatory, and motivational processes.
Functional characterization of Mousterian tools from the Caucasus using comprehensive use-wear and residue analysis
Authors: Doronicheva E. V. , Golovanova L. V. , Kostina J. V. , Legkov S. A. , Poplevko G. N. , Revina E. I. , Rusakova O. Y. , Doronichev V. B.
Published: October 2022

The authors discuss functional characterization of Mousterian tools on the basis of their use-wear and residue analysis of five lithic tools from Mezmaiskaya cave and Saradj-Chuko grotto in the North Caucasus. The results represent the first comprehensive use-wear and residue analysis carried out on Mousterian stone artefacts in the Caucasus. This study unequivocally confirms the use of bitumen for hafting stone tools in two different Middle Paleolithic cultural contexts defined in the Caucasus, Eastern Micoquian and Zagros Mousterian.
Retinal circulation time/arm-to-retina time ratio in the fluorescein angiography to evaluate retina-specific hemodynamics
Authors: Mushiga Yasuaki , Nagai Norihiro , Ozawa Yoko
Published: October 2022

To evaluate dynamic circulatory flow in the retinal or choroidal circulatory disease, we retrospectively reviewed medical charts of 128 eyes of 128 patients who underwent video recorded fluorescein angiography (FA), at Department of Ophthalmology, St Luke’s International Hospital, between April and September 2020. Mean age was 64.2 ± 14.0 (range 37–93) years, and 87 (67.9%) patients were men. Mean arm-to-retina (AR) time was 16.2 ± 4.1 s, and mean retinal circulation (RC) time was 10.9 ± 3.3 s. Mean RC time/AR time (RC/AR) ratio was 0.69 ± 0.22. AR time was correlated with age, whereas RC time was not. RC time was positively correlated with AR time (R = 0.360, P = 0.017). Moreover, mean RC time was significantly longer, and RC/AR ratio was greater, in the retinal-disease group after adjusting for age and sex. Patients who had an RC/AR ratio ≥ 0.8 more frequently presented with retinal diseases. RC time and RC/AR ratio were negatively correlated with systolic blood pressure only in the retinal-disease group. Given that AR time reflects systemic hemodynamics, RC time, which reflects local circulatory fluency, was influenced by the systemic circulatory condition. Moreover, RC/AR ratio revealed that circulatory changes peculiar to the retina may also be involved in retinal-disease pathogenesis. This study may help elucidate the mechanisms of retinal diseases and assist in diagnosis, although further studies are required.
Association of KCNJ6 rs2070995 and methadone response for pain management in advanced cancer at end-of-life
Authors: Ozberk Deniz , Haywood Alison , Sutherland Heidi G. , Yu Chieh , Albury Cassie L. , Zunk Mathew , George Rani , Good Phillip , Griffiths Lyn R. , Hardy Janet , Haupt Larisa M.
Published: October 2022

Opioids are the therapeutic agents of choice to manage moderate to severe pain in patients with advanced cancer, however the unpredictable inter-individual response to opioid therapy remains a challenge for clinicians. While studies are few, the KCNJ6 gene is a promising target for investigating genetic factors that contribute to pain and analgesia response. This is the first association study on polymorphisms in KCNJ6 and response to methadone for pain management in advanced cancer. Fifty-four adult patients with advanced cancer were recruited across two study sites in a prospective, open label, dose individualisation study. Significant associations have been previously shown for rs2070995 and opioid response in opioid substitution therapy for heroin addiction and studies in chronic pain, with mixed results seen in postoperative pain. In this study, no associations were shown for rs2070995 and methadone dose or pain score, consistent with other studies conducted in patients receiving opioids for pain in advanced cancer. There are many challenges in conducting studies in advanced cancer with significant attrition and small sample sizes, however it is hoped that the results of our study will contribute to the evidence base and allow for continued development of gene-drug dosing guidelines for clinicians.
Autotoxicity of Ambrosia artemisiifolia and Ambrosia trifida and its significance for the regulation of intraspecific populations density
Authors: Su Pei , Liu Xuelian , Wang Ruili , Liu Tong , Zhao Wenxuan , Sun Mingming , Wang Hanyue , Liu Yunxiao , Wu Qiang
Published: October 2022

Ambrosia artemisiifolia and Ambrosia trifida are annual invasive plants that cause serious harm to agriculture, animal husbandry, and human health. Based on the important characteristic of high-density, cluster distribution of their populations, it is speculated that its autotoxins have an effect on density regulation. This study explored the regulation of autotoxicity on intraspecific density. We used water extracts from two plants to compare and verify the autotoxicity of seed germination, analysed the components of autotoxins. The results showed that A. artemisiifolia and A. trifida had significant autotoxicity, and the highest inhibition rates on seed germination were 27.21% and 77.94%, respectively; ultra-performance liquid chromatography tandem mass spectrometry analysis revealed that chlorogenic acid, caffeic acid, p-coumaric acid, and vanillin were the main autotoxins of the two plants. After the seeds were washed with water, the germination recovery rate of seeds increased with the increased of inhibition degree of autotoxins treatment. Therefore, this study verified the autotoxicity of A. artemisiifolia and A. trifida, which can promote and inhibit the seed germination of A. artemisiifolia and A. trifida to regulate intraspecific competition.
Determining the potential distribution of Oryctes monoceros and Oryctes rhinoceros by combining machine-learning with high-dimensional multidisciplinary environmental variables
Authors: Aidoo Owusu Fordjour , Ding Fangyu , Ma Tian , Jiang Dong , Wang Di , Hao Mengmeng , Tettey Elizabeth , Andoh-Mensah Sebastian , Ninsin Kodwo Dadzie , Borgemeister Christian
Published: October 2022

The African coconut beetle Oryctes monoceros and Asiatic rhinoceros beetle O. rhinoceros have been associated with economic losses to plantations worldwide. Despite the amount of effort put in determining the potential geographic extent of these pests, their environmental suitability maps have not yet been well established. Using MaxEnt model, the potential distribution of the pests has been defined on a global scale. The results show that large areas of the globe, important for production of palms, are suitable for and potentially susceptible to these pests. The main determinants for O. monoceros distribution were; temperature annual range, followed by land cover, and precipitation seasonality. The major determinants for O. rhinoceros were; temperature annual range, followed by precipitation of wettest month, and elevation. The area under the curve values of 0.976 and 0.975, and True skill statistic values of 0.90 and 0.88, were obtained for O. monoceros and O. rhinoceros, respectively. The global simulated areas for O. rhinoceros (1279.00 × 104 km2) were more than that of O. monoceros (610.72 × 104 km2). Our findings inform decision-making and the development of quarantine measures against the two most important pests of palms.
Adaptive filtering of microseismic data for monitoring a water-conducting fractured zone in a mine
Authors: Li Hongjiang , Han Liang , Dong Donglin
Published: October 2022

Water-conducting fractured zones in a rock mass can cause problems in mining. Attempts have been made to monitor their development using microseismic signals. However, due to the lack of prior information, it is difficult to filter out mixed low-frequency interference with traditional denoising methods. In this work, the proposed adaptive filtering algorithm is applied after the wavelet packets are decomposed. It is based on a cross-correlation analysis. The algorithm takes a high-quality signal in the common source waveform as prior information and applies the corresponding correlation coefficients between subbands as a threshold. The algorithm was verified with simulations. The results show that low-frequency interference can be effectively suppressed by filtering. For single-frequency interference, the signal-to-noise ratio increased from − 10.18 to 13.97, and the root-mean-square error was 43.88. For multi-frequency interference, it increased from − 10.01 and − 2.63 to 13.50 and 7.99. The root-mean-square errors were 46.31 and 138.07. The narrower the main frequency band of the interference signal and the less the overlap of the main frequency band of the interference signal and the effective signal, the better the filtering effect. When the algorithm was applied to microseismic data collected in the field, the number of effective channels increased and the accuracy improved. The development of a water-conducting fractured zone in the field was consistent with the microseismic location obtained after interference was removed by the algorithm, which indicates that it is feasible to monitor a water-conducting fractured zone by analyzing microseismic waveforms with the adaptive filtering algorithm.
Adapted tensor decomposition and PCA based unsupervised feature extraction select more biologically reasonable differentially expressed genes than conventional methods
Authors: Taguchi Y-h. , Turki Turki
Published: October 2022

Tensor decomposition- and principal component analysis-based unsupervised feature extraction were proposed almost 5 and 10 years ago, respectively; although these methods have been successfully applied to a wide range of genome analyses, including drug repositioning, biomarker identification, and disease-causing genes’ identification, some fundamental problems have been identified: the number of genes identified was too small to assume that there were no false negatives, and the histogram of P values derived was not fully coincident with the null hypothesis that principal component and singular value vectors follow the Gaussian distribution. Optimizing the standard deviation such that the histogram of P values is as much as possible coincident with the null hypothesis results in an increase in the number and biological reliability of the selected genes. Our contribution was that we improved these methods so as to be able to select biologically more reasonable differentially expressed genes than the state of art methods that must empirically assume negative binomial distributions and dispersion relation, which is required for the selecting more expressed genes than less expressed ones, which can be achieved by the proposed methods that do not have to assume these.
The implications of globalization on COVID-19 vaccination in Europe
Authors: Lupu Dan , Tiganasu Ramona
Published: October 2022

Although globalization has left its mark on economic dynamism, causing conditionalities among various aspects (market openness, production networks, technological and information developments, migratory flows, international cooperation, humanitarian support, etc.), the less pleasant side of it should not be omitted, i.e. the emergence of the framework for the faster diffusion of epidemiological diseases. Thus, with the onset of the SARS-CoV-2 virus, its widespread circulation is a serious challenge for the provision of efficient solutions to combat it, especially in countries with fragile health systems, poor institutional quality and lack of resources. In this paper we aim to investigate the implications of globalization on the COVID-19 vaccination of the population. The period under analysis is January 1, 2021–January 1, 2022, using montly data, and the object of our study are 48 European states. To capture the relationship between globalization and the vaccination rate, we applied regression models, including a number of factors that may influence the progress of vaccination. In order to test the robustness of the results, the two-stage least squares (2SLS) regressions was used. The regression models developed underlined that globalization impacts the degree of vaccination. More globalized economies are more competitive in COVID-19 management, and the significance of this effect comes from better interconnection in global markets and easier access to medical discoveries. At the same time, countries with a higher vaccination rate are associated with higher levels of development. Based on the results obtained, we proposed some policy recommendations to increase the propensity to vaccinate, ensure equity in the distribution of vaccines and provide financial support to developing countries.
Odds-ratio network for postoperative factors revealing differences in the 2-year longitudinal pattern of satisfaction between women and men after total knee arthroplasty
Authors: Gallo J. , Kriegova E. , Radvansky M. , Sloviak M. , Kudelka M.
Published: October 2022

Timely and accurate assessments of the factors influencing satisfaction, a key indicator of success in primary total knee arthroplasty (TKA), may help improve TKA outcomes. Here we performed the longitudinal trend analysis of relation between satisfaction and 12 postoperative factors, which positively or negatively influence the patient satisfaction 2 years after TKA. In a real-world registry cohort (women/men: 1121/650), we showed similarities and differences between women and men in the contribution of postoperative factors to satisfaction 2 years after TKA as assessed by odds-ratio-similarity network. In men, the strongest negative factors were pain and complications, followed by mechanical problems. In women, the strongest negative factors were the pain and knee instability, followed by other mechanical problems, complications and low levels of sports activity. In both sexes, physical activity and the Knee Society Score (general and functional) influenced positively satisfaction; long-distance walking was associated with satisfaction only in women. A trend analysis revealed a reduction in the strength of satisfaction-related factors over 2 years of check-ups, particularly in women. Our study demonstrates that the key check-up for assessing the evolution of satisfaction in the 2 years after TKA was at 3 months in both sexes.
The iron-sulfur cluster is essential for DNA binding by human DNA polymerase ε
Authors: Lisova Alisa E. , Baranovskiy Andrey G. , Morstadt Lucia M. , Babayeva Nigar D. , Stepchenkova Elena I. , Tahirov Tahir H.
Published: October 2022

DNA polymerase ε (Polε) is a key enzyme for DNA replication in eukaryotes. Recently it was shown that the catalytic domain of yeast Polε (PolεCD) contains a [4Fe-4S] cluster located at the base of the processivity domain (P-domain) and coordinated by four conserved cysteines. In this work, we show that human PolεCD (hPolεCD) expressed in bacterial cells also contains an iron-sulfur cluster. In comparison, recombinant hPolεCD produced in insect cells contains significantly lower level of iron. The iron content of purified hPolECD samples correlates with the level of DNA-binding molecules, which suggests an important role of the iron-sulfur cluster in hPolε interaction with DNA. Indeed, mutation of two conserved cysteines that coordinate the cluster abolished template:primer binding as well as DNA polymerase and proofreading exonuclease activities. We propose that the cluster regulates the conformation of the P-domain, which, like a gatekeeper, controls access to a DNA-binding cleft for a template:primer. The binding studies demonstrated low affinity of hPolεCD to DNA and a strong effect of salt concentration on stability of the hPolεCD/DNA complex. Pre-steady-state kinetic studies have shown a maximal polymerization rate constant of 51.5 s−1 and a relatively low affinity to incoming dNTP with an apparent KD of 105 µM.